Skip to main content

Interleukin (IL)-7 Signaling in the Tumor Microenvironment

  • Chapter
  • First Online:
Tumor Microenvironment

Abstract

Interleukin (IL)-7 plays an important immunoregulatory role in different types of cells. Therefore, it attracts researcher’s attention, but despite the fact, many aspects of its modulatory action, as well as other functionalities, are still poorly understood. The review summarizes current knowledge on the interleukin-7 and its signaling cascade in context of cancer development. Moreover, it provides a cancer-type focused description of the involvement of IL-7 in solid tumors, as well as hematological malignancies.

The interleukin has been discovered as a growth factor crucial for the early lymphocyte development and supporting the growth of malignant cells in certain leukemias and lymphomas. Therefore, its targeting has been explored as a treatment modality in hematological malignancies, while the unique ability to expand lymphocyte populations selectively and without hyperinflammation has been used in experimental immunotherapies in patients with lymphopenia. Ever since the early research demonstrated a reduced growth of solid tumors in the presence of IL-7, the interleukin application in boosting up the anticancer immunity has been investigated. However, a growing body of evidence indicative of IL-7 upregulation in carcinomas, facilitating tumor growth and metastasis and aiding drug-resistance, is accumulating. It therefore becomes increasingly apparent that the response to the IL-7 stimulus strongly depends on cell type, their developmental stage, and microenvironmental context. The interleukin exerts its regulatory action mainly through phosphorylation events in JAK/STAT and PI3K/Akt pathways, while the significance of MAPK pathway seems to be limited to solid tumors. Given the unwavering interest in IL-7 application in immunotherapy, a better understanding of interleukin role, source in tumor microenvironment, and signaling pathways, as well as the identification of cells that are likely to respond should be a research priority.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sportès C, Babb RR, Krumlauf MC et al (2010) Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clin Cancer Res 16:727–735

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Bednarz-Misa I, Diakowska D, Krzystek-Korpacka M (2019) Local and systemic IL-7 concentration in gastrointestinal-tract cancers. Medicina (Kaunas) 55:E262

    Article  Google Scholar 

  3. Al-Rawi MAA, Rmali K, Watkins G et al (2004) Aberrant expression of interleukin-7 (IL-7) and its signalling complex in human breast cancer. Eur J Cancer 40:494–502

    Article  CAS  PubMed  Google Scholar 

  4. Cui L, Fu J, Pang JC-S et al (2012) Overexpression of IL-7 enhances cisplatin resistance in glioma. Cancer Biol Ther 13:496–503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mengus C, Le Magnen C, Trella E et al (2011) Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer. J Transl Med 9:162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ming J, Zhang Q, Qiu X et al (2009) Interleukin 7/interleukin 7 receptor induce c-Fos/c-Jun-dependent vascular endothelial growth factor-D up-regulation: a mechanism of lymphangiogenesis in lung cancer. Eur J Cancer 45:866–873

    Article  CAS  PubMed  Google Scholar 

  7. Suzuki K, Kadota K, Sima CS et al (2013) Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor β2 (IL-12Rβ2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence. J Clin Oncol 31:490–498

    Article  CAS  PubMed  Google Scholar 

  8. Kadota K, Yeh YC, Villena-Vargas J et al (2015) Tumor budding correlates with the protumor immune microenvironment and is an independent prognostic factor for recurrence of stage I lung adenocarcinoma. Chest 148:711–721

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kim MJ, Choi SK, Hong SH et al (2018) Oncogenic IL7R is downregulated by histone deacetylase inhibitor in esophageal squamous cell carcinoma via modulation of acetylated FOXO1. Int J Oncol 53:395–403

    PubMed  Google Scholar 

  10. Jiang H, Yang H, Wang H et al (2018) Elevated IL-7Rα is linked to recurrence and poorer survival of gastric adenocarcinoma. Int J Clin Exp Pathol 11:1645–1652

    PubMed  PubMed Central  Google Scholar 

  11. Fry TJ, Mackall CL (2005) The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J Immunol 174:6571–6576

    Article  CAS  PubMed  Google Scholar 

  12. Jiang Q, Li WQ, Aiello FB et al (2005) Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev 16:513–533

    Article  CAS  PubMed  Google Scholar 

  13. Kim GY, Hong C, Park J-H (2011) Seeing is believing: illuminating the source of in vivo interleukin-7. Immune Net 11:1–10

    Article  CAS  Google Scholar 

  14. Lundström W, Fewkes N, Mackall CL (2012) IL-7 in human health and disease. Semin Immunol 24:218–224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Oliveira ML, Akkapeddi P, Ribeiro D et al (2019) IL-7R-mediated signaling in T-cell acute lymphoblastic leukemia: an update. Adv Biol Regul 71:88–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gao J, Zhao L, Wan YY et al (2015) Mechanism of action of IL-7 and its potential applications and limitations in cancer immunotherapy. Int J Mol Sci 16:10267–10280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lin J, Zhu Z, Xiao H et al (2017) The role of IL-7 in immunity and cancer. Anticancer Res 37:963–967

    Article  CAS  PubMed  Google Scholar 

  18. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  19. Vudattu NK, Magalhaes I, Hoehn H et al (2009) Expression analysis and functional activity of interleukin-7 splice variants. Genes Immun 10:132–140

    Article  CAS  PubMed  Google Scholar 

  20. Park LS, Friend DJ, Schmierer AE et al (1990) Murine interleukin 7 (IL-7) receptor. Characterization on an IL-7-dependent cell line. J Exp Med 171:1073–1089

    Article  CAS  PubMed  Google Scholar 

  21. Girard D, Beaulieu AD (1997) Absence of the IL-7 receptor component CDw127 indicates that gamma(c) expression alone is insufficient for IL-7 to modulate human neutrophil responses. Clin Immunol Immunopathol 83:264–271

    Article  CAS  PubMed  Google Scholar 

  22. Akashi K, Traver D, Miyamoto T, Weissman IL (2000) A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404:193–197

    Article  CAS  PubMed  Google Scholar 

  23. Meier D, Bornmann C, Chappaz S et al (2007) Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26:643–654

    Article  CAS  PubMed  Google Scholar 

  24. Iolyeva M, Aebischer D, Proulx ST et al (2013) Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage. Blood 122:2271–2281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Onder L, Narang P, Scandella E et al (2012) IL-7-producing stromal cells are critical for lymph node remodeling. Blood 120:4675–4683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rich BE, Campos-Torres J, Tepper RI et al (1993) Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice. J Exp Med 177:305–316

    Article  CAS  PubMed  Google Scholar 

  27. Overell RW, Clark L, Lynch D et al (1991) Interleukin-7 retroviruses transform pre-B cells by an autocrine mechanism not evident in Abelson murine. Mol Cell Biol 11:1590–1597

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Zamisch M, Moore-Scott B, Su DM et al (2005) Ontogeny and regulation of IL-7-expressing thymic epithelial cells. J Immunol 174:60–67

    Article  CAS  PubMed  Google Scholar 

  29. Alves NL, Goff OR-L, Huntington ND et al (2009) Characterization of the thymic IL-7 niche in vivo. Proc Natl Acad Sci U S A 106:1512–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Scupoli MT, Vinante F, Krampera M (2003) Thymic epithelial cells promote survival of human T-cell acute lymphoblastic leukemia blasts: the role of interleukin-7. Haematologica 88:1229–1237

    CAS  PubMed  Google Scholar 

  31. Gray DHD, Tull D, Ueno T et al (2007) A unique thymic fibroblast population revealed by the monoclonal antibody MTS-15. J Immunol 178:4956–4965

    Article  CAS  PubMed  Google Scholar 

  32. Cordeiro Gomes A, Hara T, Lim VY et al (2016) Hematopoietic stem cell niches produce lineage-instructive signals to control multipotent progenitor differentiation. Immunity 45:1219–1231

    Article  CAS  PubMed  Google Scholar 

  33. Scupoli MT, Perbellini O, Krampera M et al (2007) Interleukin 7 requirement for survival of T-cell acute lymphoblastic leukemia and human thymocytes on bone marrow stroma. Haematologica 92:264–266

    Article  PubMed  Google Scholar 

  34. Zhang X, Tu H, Yang Y et al (2016) High IL-7 levels in the bone marrow microenvironment mediate imatinib resistance and predict disease progression in chronic myeloid leukemia. Int J Hematol 104:358–367

    Article  CAS  PubMed  Google Scholar 

  35. Weitzmann MN, Cenci S, Rifas L et al (2000) Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood 96:1873–1878

    Article  CAS  PubMed  Google Scholar 

  36. Giuliani N, Colla S, Sala R et al (2002) Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood 100:4615–4621

    Article  CAS  PubMed  Google Scholar 

  37. Kröncke R, Loppnow H, Flad HD et al (1996) Human follicular dendritic cells and vascular cells produce interleukin-7: a potential role for interleukin-7 in the germinal center reaction. Eur J Immunol 26:2541–2544

    Article  PubMed  Google Scholar 

  38. Takakuwa T, Nomura S, Matsuzuka F et al (2000) Expression of interleukin-7 and its receptor in thyroid lymphoma. Lab Investig 80:1483–1490

    Article  CAS  PubMed  Google Scholar 

  39. Link A, Vogt TK, Favre S et al (2007) Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat Immunol 8:1255–1265

    Article  CAS  PubMed  Google Scholar 

  40. Fujihashi K, Kawabata S, Hiroi T (1996) Interleukin 2 (IL-2) and interleukin 7 (IL-7) reciprocally induce IL-7 and IL-2 receptors on gamma delta T-cell receptor-positive intraepithelial lymphocytes. Proc Natl Acad Sci U S A 93:3613–3618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sorg RV, McLellan AD, Hock BD et al (1998) Human dendritic cells express functional interleukin-7. Immunobiology 198:514–526

    Article  CAS  PubMed  Google Scholar 

  42. de Saint-Vis B, Fugier-Vivier I, Massacrier C et al (1998) The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation. J Immunol 160:1666–1676

    Article  PubMed  Google Scholar 

  43. Mumprecht S, Schürch C, Scherrer S et al (2010) Chronic myelogenous leukemia maintains specific CD8(+) T cells through IL-7 signaling. Eur J Immunol 40:2720–2730

    Article  CAS  PubMed  Google Scholar 

  44. Di Carlo E, D’Antuono T, Pompa P et al (2009) The lack of epithelial interleukin-7 and BAFF/BLyS gene expression in prostate cancer as a possible mechanism of tumor escape from immunosurveillance. Clin Cancer Res 15:2979–2987

    Article  PubMed  Google Scholar 

  45. Madrigal-Estebas L, McManus R, Byrne B et al (1997) Human small intestinal epithelial cells secrete interleukin-7 and differentially express two different interleukin-7 mRNA transcripts: implications for extrathymic T-cell differentiation. Hum Immunol 58:83–90

    Article  CAS  PubMed  Google Scholar 

  46. Al-Rawi MAA, Rmali K, Mansel RE et al (2004) Interleukin 7 induces the growth of breast cancer cells through a Wortmannin-sensitive pathway. Br J Surg 91:61–68

    Article  CAS  PubMed  Google Scholar 

  47. Qu H, Zou Z, Pan Z et al (2016) IL-7/IL-7 receptor axis stimulates prostate cancer cell invasion and migration via AKT/NF-κB pathway. Int Immunopharmacol 40:203–210

    Article  PubMed  CAS  Google Scholar 

  48. Heufler C, Topar G, Grasseger A et al (1993) Interleukin 7 is produced by murine and human keratinocytes. J Exp Med 178:1109–1114

    Article  CAS  PubMed  Google Scholar 

  49. Long D, Blake S, Song XY et al (2008) Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13. Arthritis Res Ther 10:R23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Moors M, Vudattu NK, Abel J et al (2010) Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human neural progenitor cells. Genes Immun 11:11–20

    Article  CAS  PubMed  Google Scholar 

  51. Szot PA, Franklin DP, Figlewicz TP et al (2017) Multiple lipopolysaccharide (LPS) injections alters interleukin 6 (IL-6), IL-7, IL-10 and IL-6 and IL-7 receptor mRNA in CNS and spleen. Neuroscience 355:9–21

    Article  CAS  PubMed  Google Scholar 

  52. Jana M, Mondal S, Jana A et al (2014) Interleukin-12 (IL-12), but not IL-23, induces the expression of IL-7 in microglia and macrophages: implications for multiple sclerosis. Immunology 141:549–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mattei S, Colombo MP, Melani C et al (1994) Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. Int J Cancer 56:853–857

    Article  CAS  PubMed  Google Scholar 

  54. Kong F, Hu W, Zhou K et al (2016) Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells. J Exp Clin Cancer Res 35:172

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Whipple CA, Boni A, Fisher JL et al (2016) The mitogen-activated protein kinase pathway plays a critical role in regulating immunological properties of BRAF mutant cutaneous melanoma cells. Melanoma Res 26:223–235

    Article  CAS  PubMed  Google Scholar 

  56. Miller AR, McBride WH, Dubinett SM et al (1993) Transduction of human melanoma cell lines with the human interleukin-7 gene using retroviral-mediated gene transfer: comparison of immunologic properties with interleukin-2. Blood 82:3686–3694

    Article  CAS  PubMed  Google Scholar 

  57. Cattaruzza L, Gloghini A, Olivo K et al (2009) Functional coexpression of interleukin (IL)-7 and its receptor (IL-7R) on Hodgkin and Reed-Sternberg cells: involvement of IL-7 in tumor cell growth and microenvironmental interactions of Hodgkin’s lymphoma. Int J Cancer 125:1092–1101

    Article  CAS  PubMed  Google Scholar 

  58. Jian M, Yunjia Z, Zhiying D et al (2019) Interleukin 7 receptor activates PI3K/Akt/mTOR signaling pathway via downregulation of Beclin-1 in lung cancer. Mol Carcinog 58:358–365

    Article  CAS  PubMed  Google Scholar 

  59. Takuechi Y, Yamanouchi H, Yue Q et al (1998) Epithelial component of lymphoid stroma-rich Warthin’s tumour expresses interleukin (IL)-7. Histopathology 32:383–384

    Article  Google Scholar 

  60. Hahtola S, Tuomela S, Elo L et al (2006) Th1 response and cytotoxicity genes are down-regulated in cutaneous T-cell lymphoma. Clin Cancer Res 12:4812–4821

    Article  CAS  PubMed  Google Scholar 

  61. Iwata M, Graf L, Awaya N et al (2002) Functional interleukin-7 receptors (IL-7Rs) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein. Blood 100:1318–1325

    Article  CAS  PubMed  Google Scholar 

  62. Pillai M, Torok-Storb B, Iwata M (2004) Expression and function of IL-7 receptors in marrow stromal cells. Leuk Lymphoma 45:2403–2408

    Article  CAS  PubMed  Google Scholar 

  63. Musso T, Johnston JA, Linnekin D et al (1995) Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7. J Exp Med 181:1425–1431

    Article  CAS  PubMed  Google Scholar 

  64. Watanabe M, Ueno Y, Yajima T et al (1995) Interleukin-7 is produced by human intestinal epithelial-cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest 95:2945–2953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mazzucchelli R, Durum SK (2007) Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol 7:144–154

    Article  CAS  PubMed  Google Scholar 

  66. Nishida C, Kusubata K, Tashiro Y et al (2012) MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemokine/cytokine gene transcription within niche cells. Blood 119:5405–5416

    Article  CAS  PubMed  Google Scholar 

  67. Sawa Y, Arima Y, Ogura H et al (2009) Hepatic interleukin-7 expression regulates T cell responses. Immunity 30:447–457

    Article  CAS  PubMed  Google Scholar 

  68. Oshima S, Nakamura T, Namiki S et al (2004) Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells. Mol Cell Biol 24:6298–6310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Harada S, Yamamura M, Okamoto H et al (1999) Production of interleukin-7 and interleukin-15 by fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum 42:1508–1516

    Article  CAS  PubMed  Google Scholar 

  70. Saha A, Blando J, Silver E et al (2014) 6-Shogaol from dried ginger inhibits growth of prostate cancer cells both in vitro and in vivo through inhibition of STAT3 and NF-kB signaling. Cancer Prev Res (Phila) 7:627–638

    Article  CAS  Google Scholar 

  71. Trinder P, Seitzer U, Gerdes J et al (1999) Constitutive and IFN-y regulated expression of IL-7 and IL-15 in human renal cell cancer. Int J Oncol 14:23–31

    CAS  PubMed  Google Scholar 

  72. Cai YJ, Wang WS, Yang Y et al (2013) Up-regulation of intestinal epithelial cell derived IL-7 expression by keratinocyte growth factor through STAT1/IRF-1, IRF-2 pathway. PLoS One 8:e58647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tang J, Nuccie BL, Ritterman I et al (1997) TGF-beta down-regulates stromal IL-7 secretion and inhibits proliferation of human B cell precursors. J Immunol 159:117–125

    Article  CAS  PubMed  Google Scholar 

  74. Nye MD, Almada LL, Fernandez-Barrena MG et al (2014) The transcription factor GLI1 interacts with SMAD proteins to modulate transforming growth factor β-induced gene expression in a p300/CREB-binding protein-associated factor (PCAF)-dependent manner. J Biol Chem 289:15495–15506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Patin EC, Soulard D, Fleury et al (2018) Type I IFN receptor signaling controls IL7-dependent accumulation and activity of protumoral IL17A-producing γδT cells in breast cancer. Cancer Res 78:195–204

    Article  CAS  PubMed  Google Scholar 

  76. Korte A, Köchling J, Badiali L et al (2000) Expression analysis and characterization of alternatively spliced transcripts of human IL-7Ralpha chain encoding two truncated receptor proteins in relapsed childhood all. Cytokine 12:1597–1608

    Article  CAS  PubMed  Google Scholar 

  77. Michaud A, Dardari R, Charrier E et al (2010) IL-7 enhances survival of human CD56bright NK cells. J Immunother 33:382–390

    Article  CAS  PubMed  Google Scholar 

  78. Maude SL, Dolai S, Delgado-Martin C et al (2015) Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia. Blood 125:1759–1767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Cosenza L, Gorgun G, Urbano A et al (2002) Interleukin-7 receptor expression and activation in nonhaematopoietic neoplastic cell lines. Cell Signal 14:317–325

    Article  CAS  PubMed  Google Scholar 

  80. Maeurer MJ, Walter W, Martin D et al (1997) Interleukin-7 (IL-7) in colorectal cancer: IL-7 is produced by tissues from colorectal cancer and promotes preferential expansion of tumour infiltrating lymphocytes. Scand J Immunol 45:182–192

    Article  CAS  PubMed  Google Scholar 

  81. Jian M, Qingfu Z, Yanduo J (2015) Anti-lymphangiogenesis effects of a specific anti-interleukin 7 receptor antibody in lung cancer model in vivo. Mol Carcinog 54:148–155

    Article  PubMed  CAS  Google Scholar 

  82. Yang J, Zeng Z, Peng Y et al (2014) IL-7 splicing variant IL-7delta5 induces EMT and metastasis of human breast cancer cell lines MCF-7 and BT-20 through activation of PI3K/Akt pathway. Histochem Cell Biol 142:401–410

    Article  CAS  PubMed  Google Scholar 

  83. Laouar Y, Crispe IN, Flavell RA (2004) Overexpression of IL-7Rα provides a competitive advantage during early T-cell development. Blood 103:1985–1994

    Article  CAS  PubMed  Google Scholar 

  84. Cramer SD, Hixon JA, Andrews C et al (2018) Mutant IL-7Rα and mutant NRas are sufficient to induce murine T cell acute lymphoblastic leukemia. Leukemia 32:1795–1882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Henriques CM, Rino J, Nibbs RJ et al (2010) IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Ralpha in T cells. Blood 115:3269–3277

    Article  CAS  PubMed  Google Scholar 

  86. Sasson SC, Smith S, Seddiki N et al (2010) IL-7 receptor is expressed on adult pre-B-cell acute lymphoblastic leukemia and other B-cell derived neoplasms and correlates with expression of proliferation and survival markers. Cytokine 50:58–68

    Article  CAS  PubMed  Google Scholar 

  87. Mazzucchelli RI, Riva A, Durum SK (2012) The human IL-7 receptor gene: deletions, polymorphisms and mutations. Semin Immunol 24:225–230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Vitiello GAF, Losi Guembarovski R, Amarante MK et al (2018) Interleukin 7 receptor alpha Thr244Ile genetic polymorphism is associated with susceptibility and prognostic markers in breast cancer subgroups. Cytokine 103:121–126

    Article  CAS  PubMed  Google Scholar 

  89. Zenatti PP, Ribeiro D, Li W et al (2011) Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia. Nat Genet 43:932–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kim MS, Chung NG, Kim MS et al (2013) Somatic mutation of IL7R exon 6 in acute leukemias and solid cancers. Hum Pathol 44:551–555

    Article  CAS  PubMed  Google Scholar 

  91. Goodwin RG, Friend D, Ziegler SF et al (1990) Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. Cell 60:941–951

    Article  CAS  PubMed  Google Scholar 

  92. Crawley AM, Vranjkovic A, Young C et al (2010) Interleukin-4 downregulates CD127 expression and activity on human thymocytes and mature CD8+ T cells. Eur J Immunol 40:1396–1407

    Article  CAS  PubMed  Google Scholar 

  93. Cui H, Xie N, Tan Z et al (2014) The human long noncoding RNA lnc-IL7R regulates the inflammatory response. Eur J Immunol 44:2085–2095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ye Z, Xu J, Li S et al (2017) Lnc-IL7R promotes the growth of fibroblast-like synoviocytes through interaction with enhancer of zeste homolog 2 in rheumatoid arthritis. Mol Med Rep 15:1412–1418

    Article  CAS  PubMed  Google Scholar 

  95. Ding L, Ren J, Zhang D et al (2017) The TLR3 agonist inhibit drug efflux and sequentially consolidates low-dose cisplatin-based chemoimmunotherapy while reducing side effects. Mol Cancer Ther 16:1068–1079

    Article  CAS  PubMed  Google Scholar 

  96. Fan Y, Yan N, Juanjuan H et al (2018) Up-regulation of inflammation-related LncRNA-IL7R predicts poor clinical outcome in patients with cervical cancer. Biosci Rep 38:BSR20180483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Zhang F, Liang X, Pu D et al (2012) Biophysical characterization of glycosaminoglycan-IL-7 interactions using SPR. Biochimie 94:242–249

    Article  CAS  PubMed  Google Scholar 

  98. Clarke D, Katoh O, Gibbs RV et al (1995) Interaction of interleukin 7 (IL-7) with glycosaminoglycans and its biological relevance. Cytokine 7:325–330

    Article  CAS  PubMed  Google Scholar 

  99. Borghesi LA, Yamashita Y, Kincade PW (1999) Heparan sulfate proteoglycans mediate interleukin-7-dependent B lymphopoiesis. Blood 93:140–148

    Article  CAS  PubMed  Google Scholar 

  100. Fu R, Gao S, Peng F et al (2014) Relationship between abnormal osteoblasts and cellular immunity in multiple myeloma. Cancer Cell Int 14:62

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Kupsa T, Vasatova M, Karesova I, Zak P, Horacek JM (2014) Baseline serum levels of multiple cytokines and adhesion molecules in patients with acute myeloid leukemia: results of a pivotal trial. Exp Oncol 36:252–257

    CAS  PubMed  Google Scholar 

  102. Chopra V, Dinh TV, Hannigan EV (1998) Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer. Cancer Investig 16:152–159

    Article  CAS  Google Scholar 

  103. Mojtahedi Z, Khademi B, Erfani N et al (2014) Serum levels of interleukin-7 and interleukin-8 in head and neck squamous cell carcinoma. Indian J Cancer 51:227–230

    Article  CAS  PubMed  Google Scholar 

  104. Komura T, Sakai Y, Harada K et al (2015) Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact. Cancer Sci 106:672–686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Lambeck AJ, Crijns AP, Leffers N et al (2007) Serum cytokine profiling as a diagnostic and prognostic tool in ovarian cancer: a potential role for interleukin 7. Clin Cancer Res 13:2385–2391

    Article  CAS  PubMed  Google Scholar 

  106. Provatopoulou X, Georgiadou D, Sergentanis TN et al (2014) Interleukins as markers of inflammation in malignant and benign thyroid disease. Inflamm Res 63:667–674

    Article  CAS  PubMed  Google Scholar 

  107. Krzystek-Korpacka M, Zawadzki M, Neubauer K et al (2017) Elevated systemic interleukin-7 in patients with colorectal cancer and individuals at high risk of cancer: association with lymph node involvement and tumor location in the right colon. Cancer Immunol Immunother 66:171–179

    Article  CAS  PubMed  Google Scholar 

  108. Sandén E, Enríquez Pérez J, Visse E et al (2016) Preoperative systemic levels of VEGFA, IL-7, IL-17A, and TNF-β delineate two distinct groups of children with brain tumors. Pediatr Blood Cancer 63:2112–2122

    Article  PubMed  CAS  Google Scholar 

  109. Shen Q, Polom K, Williams C et al (2019) A targeted proteomics approach reveals a serum protein signature as diagnostic biomarker for resectable gastric cancer. EBioMedicine 44:322–333

    Article  PubMed  PubMed Central  Google Scholar 

  110. Krzystek-Korpacka M, Zawadzki M, Kapturkiewicz B et al (2018) Subsite heterogeneity in the profiles of circulating cytokines in colorectal cancer. Cytokine 110:435–441

    Article  CAS  PubMed  Google Scholar 

  111. Bordbar E, Malekzadeh M, Ardekani MT, Doroudchi M, Ghaderi A (2012) Serum levels of G-CSF and IL-7 in Iranian breast cancer patients. Asian Pac J Cancer Prev 13:5307–5312

    Article  PubMed  Google Scholar 

  112. Roato I, Brunetti G, Gorassini E et al (2006) IL-7 up-regulates TNF-α-dependent osteoclastogenesis in patients affected by solid tumor. PLoS One 1:e124

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Shiels MS, Pfeiffer RM, Hildesheim A et al (2013) Circulating inflammation markers and prospective risk for lung cancer. J Natl Cancer Inst 105:1871–1880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Comstock SS, Xu D, Hortos K et al (2016) Association of serum cytokines with colorectal polyp number and type in adult males. Eur J Cancer Prev 25:173–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Bussu F, Graziani C, Gallus R et al (2018) IFN-γ and other serum cytokines in head and neck squamous cell carcinomas. Acta Otorhinolaryngol Ital 38:94–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Lv M, Xiaoping X, Cai H et al (2011) Cytokines as prognstic tool in breast carcinoma. Front Biosci (Landmark Ed) 16:2515–2526

    Article  CAS  Google Scholar 

  117. Chen ZY, He WZ, Peng LX et al (2015) A prognostic classifier consisting of 17 circulating cytokines is a novel predictor of overall survival for metastatic colorectal cancer patients. Int J Cancer 136:584–592

    CAS  PubMed  Google Scholar 

  118. Lin Y, Zhang G, Zhang J et al (2013) A panel of four cytokines predicts the prognosis of patients with malignant gliomas. J Neuro-Oncol 114:199–208

    Article  CAS  Google Scholar 

  119. Cheng Y, Zheng S, Pan CT et al (2017) Analysis of aqueous humor concentrations of cytokines in retinoblastoma. PLoS One 12:e0177337

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Ortiz Franyuti D, Mitsi M, Vogel V (2017) Mechanical stretching of fibronectin fibers upregulates binding of interleukin-7. Nano Lett 18:15–25

    Article  PubMed  CAS  Google Scholar 

  121. Oritani K, Kinkade PW (1996) Identification of stromal cell products that interact with pre-B cells. J Cell Biol 134:771–782

    Article  CAS  PubMed  Google Scholar 

  122. Lai L, Goldschneider I (2001) Cutting edge: identification of a hybrid cytokine consisting of IL-7 and the beta-chain of the hepatocyte growth factor/scatter factor. J Immunol 167:3550–3554

    Article  CAS  PubMed  Google Scholar 

  123. Ariel A, Hershkoviz R, Cahdon L et al (1997) Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix-bound inte rleukin-7. Eur J Immunol 27:2562–2570

    Article  CAS  PubMed  Google Scholar 

  124. Cimbro R, Vassena L, Arthos J et al (2012) IL-7 induces expression and activation of integrin A4β7 promoting naive T-cell homing to the intestinal mucosa. Blood 120:2610–2619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Xie X, Ye D, Chen H et al (2004) Effect of interleukin-7 gene transfection into ovarian carcinoma cell line SKOV3 in vitro and in vivo. Gynecol Oncol 92:578–585

    Article  CAS  PubMed  Google Scholar 

  126. Kirnbauer B, Charvat B, Shauer E et al (1992) Modulation of intercellular adhesion molacule-1 expression on human melanocytes and melanoma cells: evidence for a regulator role of IL-6, IL-7, TNF-beta and UVB light. J Invest Dermatol 98:320–326

    Article  CAS  PubMed  Google Scholar 

  127. Zhang L, Keane MP, Zhu LX et al (2004) Interleukin-7 and transforming growth factor-beta play counter-regulatory roles in protein kinase C-delta-dependent control of fibroblast collagen synthesis in pulmonary fibrosis. J Biol Chem 279:28315–28319

    Article  CAS  PubMed  Google Scholar 

  128. Yamanaka O, Saika S, Ikeda K et al (2006) Interleukin-7 modulates extracellular matrix production and TGF-beta signaling in cultured human subconjunctival fibroblasts. Curr Eye Res 31:491–499

    Article  CAS  PubMed  Google Scholar 

  129. Yammani RR, Long D, Loeser RF (2009) Interleukin-7 stimulates secretion of S100A4 by activating the JAK/STAT signaling pathway in human articular chondrocytes. Arthritis Rheum 60:792–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Park SL, Lee EJ, Kim WJ et al (2014) p27KIP1 is involved in ERK1/2-mediated MMP-9 expression via the activation of NF-kappaB binding in the IL-7-induced migration and invasion of 5637 cells. Int J Oncol 44:1349–1356

    Article  CAS  PubMed  Google Scholar 

  131. Shochat C, Tal N, Bandapalli OR et al (2011) Gain-of-function mutations in interleukin-7 receptor-α (IL7R) in childhood acute lymphoblastic leukemias. J Exp Med 208:901–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Shochat C, Tal N, Gryshkova V et al (2014) Novel activating mutations lacking cysteine in type I cytokine receptors in acute lymphoblastic leukemia. Blood 124:106–110

    Article  CAS  PubMed  Google Scholar 

  133. Degryse S, de Bock CE, Demeyer S et al (2018) Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia. Leukemia 32:788–800

    Article  CAS  PubMed  Google Scholar 

  134. Huang M, Sharma S, Zhu LX et al (2002) IL-7 inhibits fibroblast TGF-beta production and signaling in pulmonary fibrosis. J Clin Invest 109:931–937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. van der Plas DC, Smiers F, Pouwels K et al (1996) Interleukin-7 signaling in human B cell precursor acute lymphoblastic leukemia cells and murine BAF3 cells involves activation of STAT1 and STAT5 mediated via the interleukin-7 receptor alpha chain. Leukemia 10:1317–1325

    PubMed  Google Scholar 

  136. Pike KA, Hatzihristidis T, Bussières-Marmen S et al (2017) TC-PTP regulates the IL-7 transcriptional response during murine early T cell development. Sci Rep 7:13275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Chou WC, Levy DE, Lee CK (2006) STAT3 positively regulates an early step in B-cell development. Blood 108:3005–3011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Li J, Liu J, Mao X et al (2014) IL-7 receptor blockade inhibits IL-17-producing γδ cells and suppresses melanoma development. Inflammation 37:1444–1452

    Article  CAS  PubMed  Google Scholar 

  139. Corfe SA, Paige CJ (2012) The many roles of IL-7 in B cell development; mediator of survival, proliferation and differentiation. Semin Immunol 24:198–208

    Article  CAS  PubMed  Google Scholar 

  140. Ribeiro D, Melão A, van Boxtel R et al (2018) STAT5 is essential for IL-7–mediated viability, growth, and proliferation of T-cell acute lymphoblastic leukemia cells. Blood Adv 2:2199–2213

    Article  PubMed  PubMed Central  Google Scholar 

  141. Qin JZ, Zhang CL, Kamarashev J et al (2001) Interleukin-7 and interleukin-15 regulate the expression of the bcl-2 and c-myb genes in cutaneous T-cell lymphoma cells. Blood 98:2778–2783

    Article  CAS  PubMed  Google Scholar 

  142. Melão A, Spit M, Cardoso BA et al (2016) Optimal interleukin-7 receptor-mediated signaling, cell cycle progression and viability of T-cell acute lymphoblastic leukemia cells rely on casein kinase 2 activity. Haematologica 101:1368–1379

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Zeng H, Yu M, Tan H et al (2018) Discrete roles and bifurcation of PTEN signaling and mTORC1-mediated anabolic metabolism underlie IL-7–driven B lymphopoiesis. Sci Adv 4:eaar5701

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Nagel S, Pommerenke C, Meyer C et al (2016) Deregulation of polycomb repressor complex 1 modifier AUTS2 in T-cell leukemia. Oncotarget 7:45398–45413

    Article  PubMed  PubMed Central  Google Scholar 

  145. Drake A, Kaur M, Iliopoulou BP et al (2016) Interleukins 7 and 15 maintain human T cell proliferative capacity through STAT5 signaling. PLoS One 11:e0166280

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Pallard C, Stegmann AP, van Kleffens T et al (1999) Distinct roles of the phosphatidylinositol 3-kinase and STAT5 pathways in IL-7-mediated development of human thymocyte precursors. Immunity 10:525–535

    Article  CAS  PubMed  Google Scholar 

  147. Crawley AM, Vranjkovic A, Faller E et al (2013) Jak/STAT and PI3K signaling pathways have both common and distinct roles in IL-7-mediated activities in human CD8+ T cells. J Leukoc Biol 95:117–127

    Article  PubMed  CAS  Google Scholar 

  148. Kim HK, Waickman AT, Castro E et al (2016) Distinct IL-7 signaling in recent thymic emigrants versus mature naïve T cells controls T-cell homeostasis. Eur J Immunol 46:1669–1680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Zhang X, Tu H, Yang Y et al (2019) Bone marrow-derived mesenchymal stromal cells promote resistance to tyrosine kinase inhibitors in chronic myeloid leukemia via the IL-7/JAK1/STAT5 pathway. J Biol Chem 294:12167–12179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Delgado-Martin C, Meyer LK, Huang BJ et al (2017) JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia 31:2568–2576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Ding ZC, Liu C, Cao Y et al (2016) IL-7 signaling imparts polyfunctionality and stemness potential to CD4(+) T cells. Onco Targets Ther 5:e1171445

    Google Scholar 

  152. Bi E, Ma X, Lu Y et al (2017) Foxo1 and Foxp1 play opposing roles in regulating the differentiation and antitumor activity of TH9 cells programmed by IL-7. Sci Signal 10(500):eaak9741

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Ribeiro D, Melão A, van Boxtel R et al (2018) IL-7 activates a STAT5/PIM1 axis to promote T-cell acute lymphoblastic leukemia proliferation and viability in a bcl-2-independent manner. Blood 132:914

    Article  Google Scholar 

  154. Seol MA, Kim JH, Oh K et al (2019) Interleukin-7 contributes to the invasiveness of prostate cancer cells by promoting epithelial-mesenchymal transition. Sci Rep 9:6917

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  155. Wofford JA, Wieman HL, Jacobs SR et al (2008) IL-7 promotes GLUT1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival. Blood 111:2101–2111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Goetz CA, Harmon IR, O’Neil JJ et al (2004) STAT5 activation underlies IL7 receptor-dependent B cell development. J Immunol 172:4770–4778

    Article  CAS  PubMed  Google Scholar 

  157. Zhang X, Song M, Kundu JK et al (2018) PIM kinase as an executional target in cancer. J Cancer Prev 23:109–116

    Article  PubMed  PubMed Central  Google Scholar 

  158. Hiasa M, Teramachi J, Oda A et al (2015) Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma. Leukemia 29:207–217

    Article  CAS  PubMed  Google Scholar 

  159. Patra AK, Avots A, Zahedi RP et al (2013) An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development. Nat Immunol 14:127–135

    Article  CAS  PubMed  Google Scholar 

  160. Pan M-G, Xiong Y, Chen F (2013) NFAT gene family in inflammation and cancer. Curr Mol Med 13:543–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Oestreich KJ, Yoon H, Ahmed R et al (2008) NFATc1 regulates PD-1 expression upon T cell activation. J Immunol 181:4832–4839

    Article  CAS  PubMed  Google Scholar 

  162. Tripathi MK, Deane NG, Zhu J et al (2014) NFAT transcriptional activity is associated with metastatic capacity in colon cancer. Cancer Res 74:6947–6957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Oikawa T, Nakamura A, Onishi N et al (2013) Acquired expression of NFATc1 downregulates E-cadherin and promotes cancer cell invasion. Cancer Res 73:5100–5109

    Article  CAS  PubMed  Google Scholar 

  164. Gast CE, Silk AD, Zarour L et al (2018) Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival. Sci Adv 4:eaat7828

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. Sharfe N, Dadi HK, Roifman CM (1995) JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3′ kinase. Blood 86:2077–2085

    Article  CAS  PubMed  Google Scholar 

  166. Aiello FB, Guszczynski T, Li W et al (2018) IL-7-induced phosphorylation of the adaptor Crk-like and other targets. Cell Signal 47:131–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Ghazawi FM, Faller EM, Sugden SM et al (2016) IL-7 downregulates IL-7Ra expression in human CD8 T cells by two independent mechanisms. Immunol Cell Biol 91:149–158

    Article  CAS  Google Scholar 

  168. Cornish AL, Chong MM, Davey GM et al (2003) Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other γc-dependent cytokines in peripheral T cells. J Biol Chem 278:22755–22761

    Article  CAS  PubMed  Google Scholar 

  169. Trengove MC, Ward AC (2013) SOCS proteins in development and disease. Am J Clin Exp Immunol 2:1–29

    PubMed  PubMed Central  Google Scholar 

  170. Canté-Barrett K, Spijkers-Hagelstein JA, Buijs-Gladdines JG et al (2016) MEK and PI3K-AKT inhibitors synergistically block activated IL7 receptor signaling in T-cell acute lymphoblastic leukemia. Leukemia 30:1832–1843

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  171. Barata JT, Cardoso AA, Boussiotis VA (2005) Interleukin-7 in T-cell acute lymphoblastic leukemia: an extrinsic factor supporting leukemogenesis? Leuk Lymphoma 46:483–495

    Article  CAS  PubMed  Google Scholar 

  172. Batista A, Barata JT, Raderschall E et al (2011) Targeting of active mTOR inhibits primary leukemia T cells and synergizes with cytotoxic drugs and signaling inhibitors. Exp Hematol 39:457–472

    Article  CAS  PubMed  Google Scholar 

  173. Li Y, Buijs-Gladdines JG, Canté-Barrett K et al (2016) IL-7 receptor mutations and steroid resistance in pediatric T cell acute lymphoblastic leukemia: a genome sequencing study. PLoS Med 13:e1002200

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Pan D, Liu B, Jin X et al (2012) IL-7 splicing variant IL-7delta5 induces human breast cancer cell proliferation via activation of PI3K/Akt pathway. Biochem Biophys Res Commun 422:727–731

    Article  CAS  PubMed  Google Scholar 

  175. Al-Rawi MAA, Watkins G, Mansel RE et al (2005) The effects of interleukin-7 on the lymphangiogenic properties of human endothelial cells. Int J Oncol 27:721–730

    CAS  PubMed  Google Scholar 

  176. Ksionda O, Melton AA, Bache J et al (2016) RasGRP1 overexpression in T-ALL increases basal nucleotide exchange on Ras rendering the Ras/PI3K/Akt pathway responsive to protumorigenic cytokines. Oncogene 35:3658–3668

    Article  CAS  PubMed  Google Scholar 

  177. Crawley JB, Rawlinson L, Lali FV et al (1997) T cell proliferation in response to interleukins 2 and 7 requires p38MAP kinase activation. J Biol Chem 272:15023–15027

    Article  CAS  PubMed  Google Scholar 

  178. Crawley JB, Willcocks J, Foxwell BM (1996) Interleukin-7 induces T cell proliferation in the absence of ErWMAP kinase activity. Eur J Immunol 26:2717–2723

    Article  CAS  PubMed  Google Scholar 

  179. Fleming HE, Paige CJ (2001) Pre-B cell receptor signaling mediates selective response to IL-7 at the pro-B to pre-B cell transition via an ERK/MAP kinase-dependent pathway. Immunity 15:521–531

    Article  CAS  PubMed  Google Scholar 

  180. Barata JT, Silva A, Brandao JG et al (2004) Activation of PI3K is indispensable for interleukin 7–mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells. J Exp Med 200:659–669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Kariminia A, Ivison SM, Leung VM et al (2017) Y-box-binding protein 1 contributes to IL-7-mediated survival signaling in B-cell precursor acute lymphoblastic leukemia. Oncol Lett 13:497–505

    Article  CAS  PubMed  Google Scholar 

  182. Martelli AM, Tabellini G, Ricci F et al (2012) PI3K/AKT/mTORC1 and MEK/ERK signaling in T-cell acute lymphoblastic leukemia: new options for targeted therapy. Adv Biol Regul 52:214–227

    Article  CAS  PubMed  Google Scholar 

  183. Page TH, Lali FL, Foxwell BMJ (1995) Interleukin-7 activates p56lck and p59fyn, two tyrosine kinases associated with the p90 interleukin-7 receptor in primary human T cells. Eur J Immunol 25:2956–2960

    Article  CAS  PubMed  Google Scholar 

  184. Abraham KM, Levin SD, Marth JD et al (1991) Thymic tumorigenesis induced by overexpression of p56lck. Proc Natl Acad Sci U S A 88:3977–3981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Tycko B, Smith SD, Sklar J (1991) Chromosomal translocations joining LCK and TCRB loci in human T cell leukemia. J Exp Med 174:867–873

    Article  CAS  PubMed  Google Scholar 

  186. Seckinger P, Fougereau M (1994) Activation of src family kinases in human pre-B cells by IL-7. J Immunol 153:97–109

    Article  CAS  PubMed  Google Scholar 

  187. Venkitaraman AR, Cowling RJ (1992) Interleukin 7 receptor functions by recruiting the tyrosine kinase p59fyn through a segment of its cytoplasmic tail. Proc Natl Acad Sci U S A 89:12083–12087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Li Y, Chen W, Ren J et al (2003) DF3/MUC1 signaling in multiple myeloma cells is regulated by interleukin-7. Cancer Biol Ther 2:187

    Article  PubMed  Google Scholar 

  189. Stroopinsky D, Kufe D, Avigan D (2016) MUC1 in hematological malignancies. Leuk Lymphoma 57:2489–2498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Shang S, Fang Hua F, Hu Z-W (2017) The regulation of β-catenin activity and function in cancer: therapeutic opportunities. Oncotarget 8:33972–33989

    Article  PubMed  PubMed Central  Google Scholar 

  191. Benbernou N, Muegge K, Durum SK (2000) Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7Ra. J Biol Chem 275:7060–7065

    Article  CAS  PubMed  Google Scholar 

  192. Pellegrini M, Bouillet P, Robati M (2004) Loss of Bim increases T cell production and function in interleukin 7 receptor–deficient mice. J Exp Med 200:1189–1195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Rathmell JC, Farkash EA, Gao W et al (2001) IL-7 enhances the survival and maintains the size of naive T cells. J Immunol 167:6869–6876

    Article  CAS  PubMed  Google Scholar 

  194. Khaled AR, Kim K, Hofmeister R et al (1999) Withdrawal of IL-7 induces Bax translocation from cytosol to mitochondria through a rise in intracellular pH. Proc Natl Acad Sci U S A 96:14476–14481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Kim K, Lee CK, Sayers TJ et al (1998) The trophic action of IL-7 on pro-T cells: inhibition of apoptosis of pro-T1, -T2, and -T3 cells correlates with Bcl-2 and bax levels and is independent of fas and p53 pathways. J Immunol 160:5735–5741

    Article  CAS  PubMed  Google Scholar 

  196. Karawajew L, Ruppert V, Wuchter C et al (2000) Inhibition of in vitro spontaneous apoptosis by IL-7 correlates with Bcl-2 up-regulation, cortical/mature immunophenotype, and better early cytoreduction of childhood T-cell acute lymphoblastic leukemia. Blood 96:297–306

    Article  CAS  PubMed  Google Scholar 

  197. Barata JT, Cardoso AA, Nadler LM et al (2001) Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27(kip1). Blood 98:1524–1531

    Article  CAS  PubMed  Google Scholar 

  198. Silva A, Laranjeira AB, Martins LR et al (2011) IL-7 contributes to the progression of human T-cell acute lymphoblastic leukemias. Cancer Res 71:4780–4789

    Article  CAS  PubMed  Google Scholar 

  199. Opferman JT, Letai A, Beard C et al (2003) Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 426:671–676

    Article  CAS  PubMed  Google Scholar 

  200. Li WQ, Jiang Q, Khaled AR et al (2004) Interleukin-7 inactivates the pro-apoptotic protein bad promoting T cell survival. J Biol Chem 279:29160–29166

    Article  CAS  PubMed  Google Scholar 

  201. Li WQ, Guszczynski T, Hixon JA et al (2010) Interleukin-7 regulates Bim proapoptotic activity in peripheral T-cell survival. Mol Cell Biol 30:590–600

    Article  PubMed  CAS  Google Scholar 

  202. Liu ZH, Wang MH, Ren HJ et al (2014) Interleukin 7 signaling prevents apoptosis by regulating Bcl-2 and Bax via the p53 pathway in human non-small cell lung cancer cells. Int J Clin Exp Pathol 7:870–881

    PubMed  PubMed Central  Google Scholar 

  203. Andersson A, Yang SC, Huang M et al (2009) IL-7 promotes CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer. J Immunol 182:6951–6918

    Article  CAS  PubMed  Google Scholar 

  204. Wuchter C, Ruppert V, Schrappe M et al (2002) In vitro susceptibility to dexamethasone- and doxorubicin-induced apoptotic cell death in context of maturation stage, responsiveness to interleukin 7, and early cytoreduction in vivo in childhood T-cell acute lymphoblastic leukemia. Blood 2002(99):4109–4115

    Article  Google Scholar 

  205. Kimura MY, Pobezinsky LA, Guinter TI et al (2013) IL-7 signaling must be intermittent, not continuous, during CD8 T cell homeostasis to promote cell survival instead of cell death. Nat Immunol 14:143–151

    Article  CAS  PubMed  Google Scholar 

  206. Lum JJ, Schnepple DJ, Nie Z et al (2004) Differential effects of interleukin-7 and interleukin-15 on NK cell anti-human immunodeficiency virus activity. J Virol 78:6033–6042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Qin JZ, Dummer R, Burg G et al (1999) Constitutive and interleukin-7/interleukin-15 stimulated DNA binding of Myc, Jun, and novel Myc-like proteins in cutaneous T-cell lymphoma cells. Blood 93:260–267

    Article  CAS  PubMed  Google Scholar 

  208. Li WQ, Jiang Q, Aleem E et al (2006) IL-7 promotes T cell proliferation through destabilization of p27Kip1. J Exp Med 203:573–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Digel W, Schmid M, Heil G et al (1991) Human interleukin-7 induces proliferation of neoplastic cells from chronic lymphocytic leukemia and acute leukemias. Blood 78:753–759

    Article  CAS  PubMed  Google Scholar 

  210. Ming J, Jiang G, Zhang Q et al (2012) Interleukin-7 up-regulates cyclin D1 via activator protein-1 to promote proliferation of cell in lung cancer. Cancer Immunol Immunother 61:79–88

    Article  CAS  PubMed  Google Scholar 

  211. Brown VI, Fang J, Alcorn K et al (2003) Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect that is modulated by IL-7-mediated signaling. Proc Natl Acad Sci U S A 100:15113–15118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Akasaka T, Tsuji K, Kawahira H et al (1997) The role of mel-18, a mammalian Polycomb group gene, during IL-7-dependent proliferation of lymphocyte precursors. Immunity 7:135–146

    Article  CAS  PubMed  Google Scholar 

  213. van der Lugt NMT, Domen J, Linders K et al (1994) Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev 8:757–769

    Article  PubMed  Google Scholar 

  214. Hartzell C, Ksionda O, Lemmens E et al (2013) Dysregulated RasGRP1 responds to cytokine receptor input in T cell leukemogenesis. Sci Signal 6:ra21

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  215. Shaw LM (2011) The insulin receptor substrate (IRS) proteins at the intersection of metabolism and cancer. Cell Cycle 10:1750–1756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Bauer DE, Harris MH, Plas DR et al (2004) Cytokine stimulation of aerobic glycolysis in hematopoietic cells exceeds proliferative demand. FASEB J 18:1303–1305

    Article  CAS  PubMed  Google Scholar 

  217. Silva A, Gírio A, Cebola I et al (2011) Intracellular reactive oxygen species are essential for PI3K/Akt/mTOR-dependent IL-7-mediated viability of T-cell acute lymphoblastic leukemia cells. Leukemia 25:960–967

    Article  CAS  PubMed  Google Scholar 

  218. Csibi A, Blenis J (2011) Appetite for destruction: the inhibition of glycolysis as a therapy for tuberous sclerosis complex-related tumors. BMC Biol 9:69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Pearson C, Silva A, Seddon B (2012) Exogenous amino acids are essential for interleukin-7 induced CD8 T cell growth. PLoS One 7:e33998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Cui G, Staron MM, Gray SM et al (2015) IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity. Cell 161:750–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Dongre A, Weinberg RA (2019) New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 20:69–84

    Article  CAS  PubMed  Google Scholar 

  222. Shilo A, Siegfried Z, Karni R (2015) The role of splicing factors in deregulation of alternative splicing during oncogenesis and tumor progression. Mol Cell Oncol 2:e970955

    Article  PubMed  CAS  Google Scholar 

  223. Fei F, Qu J, Zhang M et al (2017) S100A4 in cancer progression and metastasis: a systematic review. Oncotarget 8:73219–73239

    Article  PubMed  PubMed Central  Google Scholar 

  224. Cen B, Xiong Y, Song JH et al (2014) The Pim-1 protein kinase is an important regulator of MET receptor tyrosine kinase levels and signaling. Mol Cell Biol 34:2517–2532

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  225. Goossens S, Radaelli E, Blanchet O et al (2015) ZEB2 drives immature T-cell lympho-blastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor sig-nalling. Nat Commun 6:5794

    Article  CAS  PubMed  Google Scholar 

  226. Dubinett SM, Huang M, Dhanani S et al (1995) Down-regulation of murine fibrosarcoma transforming growth factor-βl expression by interleukin 7. J Natl Cancer Inst 87:593–597

    Article  CAS  PubMed  Google Scholar 

  227. Finke S, Trojanek B, Moller P et al (1997) Increase of sensitivity of primary human melanoma cells transfected with interleukin-7 gene to autologous and allogenic immunologic effect cells. Cancer Gene Ther 4:260–268

    CAS  PubMed  Google Scholar 

  228. Rutto KV, Lyamina IV, Kudryavtsev IV et al (2016) Regulation of vascular endothelial growth factor (VEGF) production by mouse thymic epithelial cell lines. Tsitologiia 58:436–443

    CAS  PubMed  Google Scholar 

  229. Ock C-Y, Nam A-R, Bang J-H et al (2015) The distinct signatures of VEGF and soluble VEGFR2 increase prognostic implication in gastric cancer. Am J Cancer Res 5:3376–3388

    CAS  PubMed  PubMed Central  Google Scholar 

  230. Al-Rawi MAA, Watkins G, Mansel RE et al (2005) Interleukin 7 upregulates vascular endothelial growth factor D in breast cancer cells and induces lymphangiogenesis in vivo. Br J Surg 92:305–310

    Article  CAS  PubMed  Google Scholar 

  231. Sharma S, Batra RK, Yang SC et al (2003) Interleukin-7 gene-modified dendritic cells reduce pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma. Hum Gene Ther 14:1511–1524

    Article  CAS  PubMed  Google Scholar 

  232. Gou HF, Huang J, Shi HS et al (2014) Chemo-immunotherapy with oxaliplatin and interleukin-7 inhibits colon cancer metastasis in mice. PLoS One 9:e85789

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  233. Zhao YP, Chen G, Feng B et al (2007) Microarray analysis of gene expression profile of multidrug resistance in pancreatic cancer. Chin Med J 120:1743–1752

    Article  CAS  PubMed  Google Scholar 

  234. Aoki T, Tashiro K, Miyatake S et al (1992) Expression of murine interleukin 7 in a murine glioma cell line results in reduced tumorigenicity in vivo. Proc Natl Acad Sci U S A 89:3850–3854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Sharma S, Wang J, Huang M et al (1996) Interleukin-7 gene transfer in non-small cell lung cancer decreases tumor proliferation, modifies cell surface molecule expression, and enhances antitumor reactivity. Cancer Gene Ther 3:302–313

    CAS  PubMed  Google Scholar 

  236. Hock H, Dorsch M, Diamantstein T et al (1991) Interleukin 7 induces CD4 + T cell-dependent tumor rejection. J Exp Med 174:1291–1298

    Article  CAS  PubMed  Google Scholar 

  237. McBride WH, Thacker JD, Comora S et al (1992) Genetic modification of a murine fibrosarcoma to produce interleukin 7 stimulates host cell infiltration and tumor immunity. Cancer Res 52:3931–3937

    CAS  PubMed  Google Scholar 

  238. Gunnarsson S, Bexell D, Svensson A et al (2010) Intratumoral IL-7 delivery by mesenchymal stromal cells potentiates IFNgamma-transduced tumor cell immunotherapy of experimental glioma. J Neuroimmunol 218:140–144

    Article  CAS  PubMed  Google Scholar 

  239. Dwyer CJ, Knochelmann HM, Smith AS et al (2019) Fueling cancer immunotherapy with common gamma chain cytokines. Front Immunol 10:263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Sica D, Rayman P, Stanley J et al (1993) Interleukin 7 enhances the proliferation and effector function of tumor-infiltrating lymphocytes from renal-cell carcinoma. Int J Cancer 53:941–947

    Article  CAS  PubMed  Google Scholar 

  241. Yuan CH, Yang XQ, Zhu CL et al (2014) Interleukin-7 enhances the in vivo anti-tumor activity of tumor-reactive CD8+ T cells with induction of IFN-gamma in a murine breast cancer model. Asian Pac J Cancer Prev 15:265–271

    Article  PubMed  Google Scholar 

  242. Tang JC, Shen GB, Wang SM et al (2014) IL-7 inhibits tumor growth by promoting T cell-mediated antitumor immunity in Meth A model. Immunol Lett 158:159–166

    Article  CAS  PubMed  Google Scholar 

  243. Ditonno P, Tso CL, Sakata T et al (1992) Regulatory effects of interleukin-7 on renal tumor infiltrating lymphocytes. Urol Res 20:205–210

    Article  CAS  PubMed  Google Scholar 

  244. Lamberti A, Petrella A, Pascale M et al (2004) Activation of NF-kB/Rel transcription factors in human primary peripheral blood mononuclear cells by interleukin 7. Biol Chem 385:415–417

    Article  CAS  PubMed  Google Scholar 

  245. Alderson MR, Tough TW, Ziegler SF et al (1991) Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes. J Exp Med 173:923–930

    Article  CAS  PubMed  Google Scholar 

  246. Ziegler SF, Tough TW, Franklin TL et al (1991) Induction of macrophage inflammatory protein-I f3 gene expression in human monocytes by lipopolysaccharide and IL-7. J Immunol 147:2234–2239

    Article  CAS  PubMed  Google Scholar 

  247. Maimela NR, Liu S, Zhang Y (2019) Fates of CD8+ T cells in tumor microenvironment. Comput Struct Biotechnol J 17:1–13

    Article  CAS  PubMed  Google Scholar 

  248. Andersson A, Srivastava MK, Harris-White M et al (2011) Role of CXCR3 ligands in IL-7/IL-7Rα-Fc mediated antitumor activity in lung cancer. Clin Cancer Res 17:3660–3672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Choi YW, Kang MC, Seo YB et al (2016) Intravaginal administration of Fc-fused IL7 suppresses the cervicovaginal tumor by recruiting HPV DNA vaccine-induced CD8 T cells. Clin Cancer Res 22(23):5898–5908

    Article  CAS  PubMed  Google Scholar 

  250. Huang AYC, Golumbek P, Ahmadzadeh M et al (1994) Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science (New York, NY) 264:961–965

    Article  CAS  Google Scholar 

  251. Schroten-Loef C, de Ridder CM, Reneman S et al (2008) A prostate cancer vaccine comprising whole cells secreting IL-7, effective against subcutaneous challenge, requires local GM-CSF for intra-prostatic efficacy. Cancer Immunol Immunother 58:373–381

    Article  PubMed  CAS  Google Scholar 

  252. Lee AJ, Zhou X, Chang M et al (2010) Regulation of natural killer T-cell development by deubiquitinase CYLD. EMBO J 29:1600–1612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Dubinett SM, Huang M, Dhanani S et al (1993) Down-regulation of macrophage transforming growth factor-beta messenger RNA expression by IL-7. J Immunol 151:6670–6680

    Article  CAS  PubMed  Google Scholar 

  254. Sin JI, Kim J, Pachuk C et al (2000) Interleukin 7 can enhance antigen-specific cytotoxic-T-lymphocyte and/or Th2-type immune responses in vivo. Clin Diagn Lab Immunol 7:751–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Tormoen GW, Crittenden MR, Gough MJ (2018) Role of the immunosuppressive microenvironment in immunotherapy. Adv Radiat Oncol 3:520–526

    Article  PubMed  PubMed Central  Google Scholar 

  256. Reina M, Espel E (2017) Role of LFA-1 and ICAM-1 in cancer. Cancers (Basel) 9:153

    Article  CAS  Google Scholar 

  257. Kinter AL, Godbout EJ, McNally JP et al (2008) The common γδ-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J Immunol 181:6738–6746

    Article  CAS  PubMed  Google Scholar 

  258. Bardhan K, Anagnostou T, Boussiotis VA (2016) The PD1:PD-L1/2 pathway from discovery to clinical implementation. Front Immunol 7:550

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  259. Myklebust JH, Irish JM, Brody J et al (2013) High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells. Blood 121:1367–1376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  260. Pfannenstiel LW, Diaz-Montero CM, Tian YF et al (2019) Immune-checkpoint blockade opposes CD8+ T-cell suppression in human and murine cancer. Cancer Immunol Res 7:510–525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Veluswamy P, Bruder D (2018) PD-1/PD-L1 pathway inhibition to restore effector functions in exhausted CD8+ T cells: chances, limitations and potential risks. Transl Cancer Res 7(Suppl 4):S530–S537

    Article  CAS  Google Scholar 

  262. Chen HC, Eling N, Martinez-Jimenez CP et al (2019) IL-7-dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti-tumour response. EMBO Rep 8:e47379

    Google Scholar 

  263. Johnson LDS, Banerjee S, Kruglov O et al (2019) Targeting CD47 in Sézary syndrome with SIRPαFc. Blood Adv 3:1145–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. Eder M, Ottmann OG, Hansen-Hagge TE et al (1990) Effects of recombinant human IL-7 on blast cell proliferation in acute lymphoblastic leukemia. Leukemia 4:533–540

    CAS  PubMed  Google Scholar 

  265. Skjønsberg C, Erikstein BK, Smeland EB et al (1991) Interleukin-7 differentiates a subgroup of acute lymphoblastic leukemias. Blood 77:2445–2450

    Article  PubMed  Google Scholar 

  266. Touw I, Pouwels K, van Agthoven T et al (1990) Interleukin-7 is a growth factor of precursor B and T acute lymphoblastic leukemia. Blood 75:2097–2101

    Article  CAS  PubMed  Google Scholar 

  267. Dibirdik I, Langlie MC, Ledbetter JA et al (1991) Engagement of interleukin-7 receptor stimulates tyrosine phosphorylation, phosphoinositide turnover, and clonal proliferation of human T-lineage acute lymphoblastic leukemia cells. Blood 78:564–570

    Article  CAS  PubMed  Google Scholar 

  268. Canté-Barrett K, Spijkers-Hagelstein JA, Buijs-Gladdines JG et al (2016) MEK and PI3K-AKT inhibitors synergistically block activated IL7 receptor signaling in T-cell acute lymphoblastic leukemia. Leukemia 30:1832–1843

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  269. Wang H, Zang C, Taing L et al (2014) NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers. Proc Natl Acad Sci U S A 111:705–710

    Article  CAS  PubMed  Google Scholar 

  270. González-García S, Toribio ML (2009) Notch 1 signalling in human T-cell development and leukemia. Ther Immunol 28:93–208

    Google Scholar 

  271. Tremblay CS, Brown FC, Collett M et al (2016) Loss-of-function mutations of dynamin 2 promote T-ALL by enhancing IL-7 signalling. Leukemia 30:1993–2001

    Article  CAS  PubMed  Google Scholar 

  272. Melão A, Spit M, Cardoso BA, Barata JT (2016) Optimal interleukin-7 receptor-mediated signaling, cell cycle progression and viability of T-cell acute lymphoblastic leukemia cells rely on casein kinase 2 activity. Haematologica 101:1368–1379

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  273. Dalloul A, Laroche L, Bagot M et al (1992) Interleukin-7 is a growth factor for Sézary lymphoma cells. J Clin Invest 90:1054–1060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Ge Z, Gu Y, Xiao L et al (2016) Co-existence of IL7R high and SH2B3 low expression distinguishes a novel high-risk acute lymphoblastic leukemia with Ikaros dysfunction. Oncotarget 7:46014–46027

    Article  PubMed  PubMed Central  Google Scholar 

  275. Nishii K, Katayama N, Miwa H et al (1999) Survival of human leukaemic B-cell precursors is supported by stromal cells and cytokines: association with the expression of bcl-2 protein. Br J Haematol 105:701–710

    Article  CAS  PubMed  Google Scholar 

  276. Scott DW, Gascoyne RD (2014) The tumour microenvironment in B cell lymphomas. Nat Rev Cancer 14:517–534

    Article  CAS  PubMed  Google Scholar 

  277. Weitzmann MN, Roggia C, Toraldo G et al (2002) Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. J Clin Invest 110:1643–1650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  278. Giuliani N, Colla S, Morandi F et al (2005) Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 106:2472–2483

    Article  CAS  PubMed  Google Scholar 

  279. D’Souza S, del Prete D, Jin S et al (2011) Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease. Blood 118:6871–6880

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  280. Storti P, Bolzoni M, Donofrio G et al (2013) Hypoxia-inducible factor (HIF)-1α suppression in myeloma cells blocks tumoral growth in vivo inhibiting angiogenesis and bone destruction. Leukemia 27:1697–1706

    Article  CAS  PubMed  Google Scholar 

  281. Aldinucci D, Lorenzon D, Olivo K et al (2004) Interactions between tissue fibroblasts in lymph nodes and Hodgkin/Reed-Sternberg cells. Leuk Lymphoma 45:1731–1739

    Article  CAS  PubMed  Google Scholar 

  282. Riedel A, Shorthouse D, Haas L et al (2016) Tumor-induced stromal reprogramming drives lymph node transformation. Nat Immunol 17:1118–1127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  283. Carrio R, Altman NH, Lopez DM (2009) Downregulation of interleukin-7 and hepatocyte growth factor in the thymic microenvironment is associated with thymus involution in tumor-bearing mice. Cancer Immunol Immunother 58:2059–2072

    Article  CAS  PubMed  Google Scholar 

  284. Mandal D, Lahiry L, Bhattacharyya A et al (2006) Tumor-induced thymic involution via inhibition of IL-7R alpha and its JAK-STAT signaling pathway: protection by black tea. Int Immunopharmacol 6:433–444

    Article  CAS  PubMed  Google Scholar 

  285. Sorrentino C, Musiani P, Pompa P et al (2011) Androgen deprivation boosts prostatic infiltration of cytotoxic and regulatory T lymphocytes and has no effect on disease-free survival in prostate cancer patients. Clin Cancer Res 17:1571–1581

    Article  CAS  PubMed  Google Scholar 

  286. Schroten C, Dits NF, Steyerberg EW et al (2012) The additional value of TGFβ1 and IL-7 to predict the course of prostate cancer progression. Cancer Immunol Immunother 61:905–910

    Article  CAS  PubMed  Google Scholar 

  287. Bednarz-Misa I, Fortuna P, Diakowska D, Jamrozik N, Krzystek-Korpacka M (2020) Distinct local and systemic molecular signatures in the esophageal and gastric cancers: possible therapy targets and biomarkers for gastric cancer. Int J Mol Sci 21:E4509

    Article  PubMed  CAS  Google Scholar 

  288. Oka M, Hirose K, Iizuka N et al (1995) Cytokine mRNA expression patterns in human esophageal cancer cell lines. J Interf Cytokine Res 15:1005–1009

    Article  CAS  Google Scholar 

  289. D’Amico L, Satolli MA, Mecca C et al (2013) Bone metastases in gastric cancer follow a RANKL-independent mechanism. Oncol Rep 29:1453–1458

    Article  PubMed  CAS  Google Scholar 

  290. Yamaoka Y, Kita M, Kodama T et al (1995) Expression of cytokine mRNA in gastric mucosa with Helicobacter pylori infection. Scand J Gastroenterol 30:1153–1159

    Article  CAS  PubMed  Google Scholar 

  291. Yu F, Tian T, Deng B et al (2019) Multi-marker analysis of genomic annotation on gastric cancer GWAS data from Chinese populations. Gastric Cancer 22:60–68

    Article  CAS  PubMed  Google Scholar 

  292. Giuntoli RL 2nd, Webb TJ, Zoso A et al (2009) Ovarian cancer-associated ascites demonstrates altered immune environment: implications for antitumor immunity. Anticancer Res 29:2875–2884

    CAS  PubMed  Google Scholar 

  293. Chang YS, Huang HD, Yeh KT et al (2016) Genetic alterations in endometrial cancer by targeted next-generation sequencing. Exp Mol Pathol 100:8–12

    Article  CAS  PubMed  Google Scholar 

  294. Espinoza JA, Jabeen S, Batra R et al (2016) Cytokine profiling of tumor interstitial fluid of the breast and its relationship with lymphocyte infiltration and clinicopathological characteristics. Onco Targets Ther 5:e1248015

    Google Scholar 

  295. Vudattu NK, Magalhaes I, Schmidt M et al (2007) Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer. Int J Cancer 121:1512–1519

    Article  CAS  PubMed  Google Scholar 

  296. Midorikawa Y, Tsutsumi S, Taniguchi H et al (2002) Identification of genes associated with dedifferentiation of hepatocellular carcinoma with expression profiling analysis. Jpn J Cancer Res 93:636–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Małgorzata Krzystek-Korpacka .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bednarz-Misa, I., Bromke, M.A., Krzystek-Korpacka, M. (2021). Interleukin (IL)-7 Signaling in the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment . Advances in Experimental Medicine and Biology, vol 1290. Springer, Cham. https://doi.org/10.1007/978-3-030-55617-4_2

Download citation

Publish with us

Policies and ethics