Skip to main content
SpringerLink
Log in

Role of Chemokines and Chemokine Receptors in Cancer

  • Chapter
  • First Online:
Cancer Immunology

Abstract

Chemokines (CKs) are small chemoattractant cytokines which regulate the process of cellular trafficking. Due to their key role in determinant biological functions associated with tumor development, they are ideal targets for investigating tumor progression, prognosis, therapy, and susceptibility. In this chapter, the mechanism through which chemokines control the different stages of oncogenesis is described. At first, a detailed description on the role of these molecules in tumor cell proliferation, survival, and metastasis implantation is provided. Then their role in the modulation of specific and innate immune responses against the tumor, along with their impact on the tumor prognosis, is discussed. Finally, we extensively reported on various studies of chemokine gene polymorphisms associated with clinical prognosis and commented on the use of chemokine-derived molecules as anticancer therapeutic tools.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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. Yoshimura T, Matsushima K, Oppenheim JJ, Leonard EJ. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol. 1987;139(3):788–93.

    CAS  PubMed  Google Scholar 

  2. Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179.

    Article  CAS  PubMed  Google Scholar 

  3. Kunkel SL, Lukacs N, Strieter RM. Chemokines and their role in human disease. Agents Actions Suppl. 1995;46:11–22.

    CAS  PubMed  Google Scholar 

  4. Kunkel SL. Through the looking glass: the diverse in vivo activities of chemokines. J Clin Invest. 1999;104(10):1333–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Taub DD, Ortaldo JR, Turcovski-Corrales SM, Key ML, Longo DL, Murphy WJ. Beta chemokines costimulate lymphocyte cytolysis, proliferation, and lymphokine production. J Leukoc Biol. 1996;59(1):81–9.

    Article  CAS  PubMed  Google Scholar 

  6. Luster AD. Chemokines--chemotactic cytokines that mediate inflammation. N Engl J Med. 1998;338(7):436–45.

    Article  CAS  PubMed  Google Scholar 

  7. Mackay CR. Chemokines: immunology’s high impact factors. Nat Immunol. 2001;2(2):95–101.

    Article  CAS  PubMed  Google Scholar 

  8. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006;354(6):610–21.

    Article  CAS  PubMed  Google Scholar 

  9. Sounni NE, Noel A. Targeting the tumor microenvironment for cancer therapy. Clin Chem. 2013;59(1):85–93.

    Article  CAS  PubMed  Google Scholar 

  10. Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res. 1970;13:1–27.

    Article  CAS  PubMed  Google Scholar 

  11. Zhou G, Lu Z, McCadden JD, Levitsky HI, Marson AL. Reciprocal changes in tumor antigenicity and antigen-specific T cell function during tumor progression. J Exp Med. 2004;200(12):1581–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kelner GS, Zlotnik A. Cytokine production profile of early thymocytes and the characterization of a new class of chemokine. J Leukoc Biol. 1995;57(5):778–81.

    Article  CAS  PubMed  Google Scholar 

  13. Zlotnik A, Yoshie O. The chemokine superfamily revisited. Immunity. 2012;36(5):705–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000;12(2):121–7.

    Article  CAS  PubMed  Google Scholar 

  15. Borrello MG, Alberti L, Fischer A, Degl’innocenti D, Ferrario C, Gariboldi M, et al. Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. Proc Natl Acad Sci U S A. 2005;102(41):14825–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med. 2007;13(10):1211–8.

    Article  CAS  PubMed  Google Scholar 

  17. Balkwill FR. The chemokine system and cancer. J Pathol. 2011;226(2):148–57.

    Article  PubMed  CAS  Google Scholar 

  18. Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell. 2004;6(5):447–58.

    Article  CAS  PubMed  Google Scholar 

  19. Yang G, Rosen DG, Zhang Z, Bast RC Jr, Mills GB, Colacino JA, et al. The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis. Proc Natl Acad Sci U S A. 2006;103(44):16472–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pivarcsi A, Muller A, Hippe A, Rieker J, van Lierop A, Steinhoff M, et al. Tumor immune escape by the loss of homeostatic chemokine expression. Proc Natl Acad Sci U S A. 2007;104(48):19055–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature. 2003;425(6955):307–11.

    Article  CAS  PubMed  Google Scholar 

  22. Katoh M. Integrative genomic analyses of CXCR4: transcriptional regulation of CXCR4 based on TGFbeta, Nodal, Activin signaling and POU5F1, FOXA2, FOXC2, FOXH1, SOX17, and GFI1 transcription factors. Int J Oncol. 2010;36(2):415–20.

    CAS  PubMed  Google Scholar 

  23. Mehta SA, Christopherson KW, Bhat-Nakshatri P, Goulet RJ Jr, Broxmeyer HE, Kopelovich L, et al. Negative regulation of chemokine receptor CXCR4 by tumor suppressor p53 in breast cancer cells: implications of p53 mutation or isoform expression on breast cancer cell invasion. Oncogene. 2007;26(23):3329–37.

    Article  CAS  PubMed  Google Scholar 

  24. Roussos ET, Condeelis JS, Patsialou A. Chemotaxis in cancer. Nat Rev Cancer. 2011;11(8):573–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 2004;64(19):7022–9.

    Article  CAS  PubMed  Google Scholar 

  26. Hernandez L, Magalhaes MA, Coniglio SJ, Condeelis JS, Segall JE. Opposing roles of CXCR4 and CXCR7 in breast cancer metastasis. Breast Cancer Res. 2011;13(6):R128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Teicher BA, Fricker SP. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res. 2010;16(11):2927–31.

    Article  CAS  PubMed  Google Scholar 

  28. Ramsey DM, McAlpine SR. Halting metastasis through CXCR4 inhibition. Bioorg Med Chem Lett. 2013;23(1):20–5.

    Article  CAS  PubMed  Google Scholar 

  29. Ploenes T, Scholtes B, Krohn A, Burger M, Passlick B, Muller-Quernheim J, et al. CC-chemokine ligand 18 induces epithelial to mesenchymal transition in lung cancer A549 cells and elevates the invasive potential. PLoS One. 2013;8(1):e53068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lee SH, Kang HY, Kim KS, Nam BY, Paeng J, Kim S, et al. The monocyte chemoattractant protein-1 (MCP-1)/CCR2 system is involved in peritoneal dialysis-related epithelial-mesenchymal transition of peritoneal mesothelial cells. Lab Investig. 2012;92(12):1698–711.

    Article  CAS  PubMed  Google Scholar 

  31. Hao M, Zheng J, Hou K, Wang J, Chen X, Lu X, et al. Role of chemokine receptor CXCR7 in bladder cancer progression. Biochem Pharmacol. 2012;84(2):204–14.

    Article  CAS  PubMed  Google Scholar 

  32. Palena C, Hamilton DH, Fernando RI. Influence of IL-8 on the epithelial-mesenchymal transition and the tumor microenvironment. Future Oncol. 2012;8(6):713–22.

    Article  CAS  PubMed  Google Scholar 

  33. Chang MC, Lee JJ, Chen YJ, Lin SI, Lin LD, Jein-Wen Liou E, et al. Lysophosphatidylcholine induces cytotoxicity/apoptosis and IL-8 production of human endothelial cells: related mechanisms. Oncotarget. 2017;8(63):106177–89.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhou N, Lu F, Liu C, Xu K, Huang J, Yu D, et al. IL-8 induces the epithelial-mesenchymal transition of renal cell carcinoma cells through the activation of AKT signaling. Oncol Lett. 2016;12(3):1915–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410(6824):50–6.

    Article  CAS  PubMed  Google Scholar 

  36. Andre F, Cabioglu N, Assi H, Sabourin JC, Delaloge S, Sahin A, et al. Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer. Ann Oncol. 2006;17(6):945–51.

    Article  CAS  PubMed  Google Scholar 

  37. Amersi FF, Terando AM, Goto Y, Scolyer RA, Thompson JF, Tran AN, et al. Activation of CCR9/CCL25 in cutaneous melanoma mediates preferential metastasis to the small intestine. Clin Cancer Res. 2008;14(3):638–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zlotnik A, Burkhardt AM, Homey B. Homeostatic chemokine receptors and organ-specific metastasis. Nat Rev Immunol. 2011;11(9):597–606.

    Article  CAS  PubMed  Google Scholar 

  39. Acosta JC, O’Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell. 2008;133(6):1006–18.

    Article  CAS  PubMed  Google Scholar 

  40. Ruan JW, Liao YC, Lua I, Li MH, Hsu CY, Chen JH. Human pituitary tumor-transforming gene 1 overexpression reinforces oncogene-induced senescence through CXCR2/p21 signaling in breast cancer cells. Breast Cancer Res. 2012;14(4):R106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Benelli R, Stigliani S, Minghelli S, Carlone S, Ferrari N. Impact of CXCL1 overexpression on growth and invasion of prostate cancer cell. Prostate. 2013;73(9):941–51.

    Article  CAS  PubMed  Google Scholar 

  42. Kitadai Y, Haruma K, Mukaida N, Ohmoto Y, Matsutani N, Yasui W, et al. Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8. Clin Cancer Res. 2000;6(7):2735–40.

    CAS  PubMed  Google Scholar 

  43. Wang B, Hendricks DT, Wamunyokoli F, Parker MI. A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 2006;66(6):3071–7.

    Article  CAS  PubMed  Google Scholar 

  44. Luppi F, Longo AM, de Boer WI, Rabe KF, Hiemstra PS. Interleukin-8 stimulates cell proliferation in non-small cell lung cancer through epidermal growth factor receptor transactivation. Lung Cancer. 2007;56(1):25–33.

    Article  CAS  PubMed  Google Scholar 

  45. Gabellini C, Trisciuoglio D, Desideri M, Candiloro A, Ragazzoni Y, Orlandi A, et al. Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. Eur J Cancer. 2009;45(14):2618–27.

    Article  CAS  PubMed  Google Scholar 

  46. Darash-Yahana M, Gillespie JW, Hewitt SM, Chen YY, Maeda S, Stein I, et al. The chemokine CXCL16 and its receptor, CXCR6, as markers and promoters of inflammation-associated cancers. PLoS One. 2009;4(8):e6695.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Balkwill F. Cancer and the chemokine network. Nat Rev Cancer. 2004;4(7):540–50.

    Article  CAS  PubMed  Google Scholar 

  48. Rubie C, Frick VO, Ghadjar P, Wagner M, Grimm H, Vicinus B, et al. CCL20/CCR6 expression profile in pancreatic cancer. J Transl Med. 2010;8:45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Shen X, Mailey B, Ellenhorn JD, Chu PG, Lowy AM, Kim J. CC chemokine receptor 9 enhances proliferation in pancreatic intraepithelial neoplasia and pancreatic cancer cells. J Gastrointest Surg. 2009;13(11):1955–62; discussion 62

    Article  PubMed  Google Scholar 

  50. Murakami T, Cardones AR, Finkelstein SE, Restifo NP, Klaunberg BA, Nestle FO, et al. Immune evasion by murine melanoma mediated through CC chemokine receptor-10. J Exp Med. 2003;198(9):1337–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wang J, Zhang X, Thomas SM, Grandis JR, Wells A, Chen ZG, et al. Chemokine receptor 7 activates phosphoinositide-3 kinase-mediated invasive and prosurvival pathways in head and neck cancer cells independent of EGFR. Oncogene. 2005;24(38):5897–904.

    Article  CAS  PubMed  Google Scholar 

  52. Xu Y, Liu L, Qiu X, Liu Z, Li H, Li Z, et al. CCL21/CCR7 prevents apoptosis via the ERK pathway in human non-small cell lung cancer cells. PLoS One. 2012;7(3):e33262.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mukaida N, Baba T. Chemokines in tumor development and progression. Exp Cell Res. 2011;318(2):95–102.

    Article  PubMed  CAS  Google Scholar 

  54. Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 2006;203(9):2201–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Coussens LM, Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science. 2013;339(6117):286–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Franciszkiewicz K, Boissonnas A, Boutet M, Combadiere C, Mami-Chouaib F. Role of chemokines and chemokine receptors in shaping the effector phase of the antitumor immune response. Cancer Res. 2012;72(24):6325–32.

    Article  CAS  PubMed  Google Scholar 

  57. Castellino F, Huang AY, Altan-Bonnet G, Stoll S, Scheinecker C, Germain RN. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature. 2006;440(7086):890–5.

    Article  CAS  PubMed  Google Scholar 

  58. Castellino F, Germain RN. Chemokine-guided CD4+ T cell help enhances generation of IL-6RalphahighIL-7Ralpha high prememory CD8+ T cells. J Immunol. 2007;178(2):778–87.

    Article  CAS  PubMed  Google Scholar 

  59. Kaiser A, Donnadieu E, Abastado JP, Trautmann A, Nardin A. CC chemokine ligand 19 secreted by mature dendritic cells increases naive T cell scanning behavior and their response to rare cognate antigen. J Immunol. 2005;175(4):2349–56.

    Article  CAS  PubMed  Google Scholar 

  60. Laoui D, Keirsse J, Morias Y, Van Overmeire E, Geeraerts X, Elkrim Y, et al. The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity. Nat Commun. 2016;7:13720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 2014;26(5):638–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Roberts EW, Broz ML, Binnewies M, Headley MB, Nelson AE, Wolf DM, et al. Critical role for CD103(+)/CD141(+) dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma. Cancer Cell. 2016;30(2):324–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Spranger S, Dai D, Horton B, Gajewski TF. Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell. 2017;31(5):711–23 e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R, Jordan S, et al. Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity. 2016;44(4):924–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Miller MJ, Hejazi AS, Wei SH, Cahalan MD, Parker I. T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node. Proc Natl Acad Sci U S A. 2004;101(4):998–1003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bousso P, Robey E. Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nat Immunol. 2003;4(6):579–85.

    Article  CAS  PubMed  Google Scholar 

  67. Asperti-Boursin F, Real E, Bismuth G, Trautmann A, Donnadieu E. CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3-kinase-independent manner. J Exp Med. 2007;204(5):1167–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hugues S, Scholer A, Boissonnas A, Nussbaum A, Combadiere C, Amigorena S, et al. Dynamic imaging of chemokine-dependent CD8+ T cell help for CD8+ T cell responses. Nat Immunol. 2007;8(9):921–30.

    Article  CAS  PubMed  Google Scholar 

  69. Friedman RS, Jacobelli J, Krummel MF. Surface-bound chemokines capture and prime T cells for synapse formation. Nat Immunol. 2006;7(10):1101–8.

    Article  CAS  PubMed  Google Scholar 

  70. Franciszkiewicz K, Le Floc’h A, Jalil A, Vigant F, Robert T, Vergnon I, et al. Intratumoral induction of CD103 triggers tumor-specific CTL function and CCR5-dependent T-cell retention. Cancer Res. 2009;69(15):6249–55.

    Article  CAS  PubMed  Google Scholar 

  71. Dustin ML. Stop and go traffic to tune T cell responses. Immunity. 2004;21(3):305–14.

    Article  CAS  PubMed  Google Scholar 

  72. Moser B, Loetscher P. Lymphocyte traffic control by chemokines. Nat Immunol. 2001;2(2):123–8.

    Article  CAS  PubMed  Google Scholar 

  73. Hojo S, Koizumi K, Tsuneyama K, Arita Y, Cui Z, Shinohara K, et al. High-level expression of chemokine CXCL16 by tumor cells correlates with a good prognosis and increased tumor-infiltrating lymphocytes in colorectal cancer. Cancer Res. 2007;67(10):4725–31.

    Article  CAS  PubMed  Google Scholar 

  74. Ohta M, Tanaka F, Yamaguchi H, Sadanaga N, Inoue H, Mori M. The high expression of Fractalkine results in a better prognosis for colorectal cancer patients. Int J Oncol. 2005;26(1):41–7.

    CAS  PubMed  Google Scholar 

  75. Salmon H, Franciszkiewicz K, Damotte D, Dieu-Nosjean MC, Validire P, Trautmann A, et al. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J Clin Invest. 2012;122(3):899–910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Boissonnas A, Licata F, Poupel L, Jacquelin S, Fetler L, Krumeich S, et al. CD8+ tumor-infiltrating T cells are trapped in the tumor-dendritic cell network. Neoplasia. 2013;15(1):85–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Engelhardt JJ, Boldajipour B, Beemiller P, Pandurangi P, Sorensen C, Werb Z, et al. Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell. 2012;21(3):402–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Boissonnas A, Fetler L, Zeelenberg IS, Hugues S, Amigorena S. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J Exp Med. 2007;204(2):345–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yona S, Kim KW, Wolf Y, Mildner A, Varol D, Breker M, et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity. 2013;38(1):79–91.

    Article  CAS  PubMed  Google Scholar 

  80. Franklin RA, Li MO. The ontogeny of tumor-associated macrophages: a new understanding of cancer-elicited inflammation. Oncoimmunology. 2014;3(9):e955346.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Conti I, Rollins BJ. CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol. 2004;14(3):149–54.

    Article  CAS  PubMed  Google Scholar 

  82. Linde N, Casanova-Acebes M, Sosa MS, Mortha A, Rahman A, Farias E, et al. Macrophages orchestrate breast cancer early dissemination and metastasis. Nat Commun. 2018;9(1):21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, et al. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 2007;67(6):2649–56.

    Article  CAS  PubMed  Google Scholar 

  84. Bakst RL, Xiong H, Chen CH, Deborde S, Lyubchik A, Zhou Y, et al. Inflammatory monocytes promote perineural invasion via CCL2-mediated recruitment and cathepsin B expression. Cancer Res. 2017;77(22):6400–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zhu Y, Herndon JM, Sojka DK, Kim KW, Knolhoff BL, Zuo C, et al. Tissue-resident macrophages in pancreatic ductal adenocarcinoma originate from embryonic hematopoiesis and promote tumor progression. Immunity. 2017;47(2):323–38 e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Bowman RL, Klemm F, Akkari L, Pyonteck SM, Sevenich L, Quail DF, et al. Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies. Cell Rep. 2016;17(9):2445–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Loyher PL, Hamon P, Laviron M, Meghraoui-Kheddar A, Goncalves E, Deng Z, et al. Macrophages of distinct origins contribute to tumor development in the lung. J Exp Med. 2018;215(10):2536–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mass E, Ballesteros I, Farlik M, Halbritter F, Gunther P, Crozet L, et al. Specification of tissue-resident macrophages during organogenesis. Science. 2016;353(6304):aaf4238.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Nesbit M, Schaider H, Miller TH, Herlyn M. Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells. J Immunol. 2001;166(11):6483–90.

    Article  CAS  PubMed  Google Scholar 

  90. Kitamura T, Qian BZ, Soong D, Cassetta L, Noy R, Sugano G, et al. CCL2-induced chemokine cascade promotes breast cancer metastasis by enhancing retention of metastasis-associated macrophages. J Exp Med. 2015;212(7):1043–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Rodero M, Marie Y, Coudert M, Blondet E, Mokhtari K, Rousseau A, et al. Polymorphism in the microglial cell-mobilizing CX3CR1 gene is associated with survival in patients with glioblastoma. J Clin Oncol. 2008;26(36):5957–64.

    Article  PubMed  Google Scholar 

  92. Rodero MP, Auvynet C, Poupel L, Combadiere B, Combadiere C. Control of both myeloid cell infiltration and angiogenesis by CCR1 promotes liver cancer metastasis development in mice. Neoplasia. 2013;15(6):641–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bonecchi R, Facchetti F, Dusi S, Luini W, Lissandrini D, Simmelink M, et al. Induction of functional IL-8 receptors by IL-4 and IL-13 in human monocytes. J Immunol. 2000;164(7):3862–9.

    Article  CAS  PubMed  Google Scholar 

  94. Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, et al. Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med. 2003;198(9):1391–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sica A, Saccani A, Bottazzi B, Bernasconi S, Allavena P, Gaetano B, et al. Defective expression of the monocyte chemotactic protein-1 receptor CCR2 in macrophages associated with human ovarian carcinoma. J Immunol. 2000;164(2):733–8.

    Article  CAS  PubMed  Google Scholar 

  96. Qiu L, Ding L, Huang J, Wang D, Zhang J, Guo B. Induction of copper/zinc-superoxide dismutase by CCL5/CCR5 activation causes tumour necrosis factor-alpha and reactive oxygen species production in macrophages. Immunology. 2009;128(1 Suppl):e325–34.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science. 2007;317(5838):666–70.

    Article  CAS  PubMed  Google Scholar 

  98. Hanna RN, Cekic C, Sag D, Tacke R, Thomas GD, Nowyhed H, et al. Patrolling monocytes control tumor metastasis to the lung. Science. 2015;350(6263):985–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Plebanek MP, Angeloni NL, Vinokour E, Li J, Henkin A, Martinez-Marin D, et al. Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche. Nat Commun. 2017;8(1):1319.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Park MH, Lee JS, Yoon JH. High expression of CX3CL1 by tumor cells correlates with a good prognosis and increased tumor-infiltrating CD8+ T cells, natural killer cells, and dendritic cells in breast carcinoma. J Surg Oncol. 2012;106(4):386–92.

    Article  CAS  PubMed  Google Scholar 

  101. Lavergne E, Combadiere B, Bonduelle O, Iga M, Gao JL, Maho M, et al. Fractalkine mediates natural killer-dependent antitumor responses in vivo. Cancer Res. 2003;63(21):7468–74.

    CAS  PubMed  Google Scholar 

  102. Lavergne E, Combadiere C, Iga M, Boissonnas A, Bonduelle O, Maho M, et al. Intratumoral CC chemokine ligand 5 overexpression delays tumor growth and increases tumor cell infiltration. J Immunol. 2004;173(6):3755–62.

    Article  CAS  PubMed  Google Scholar 

  103. Crittenden M, Gough M, Harrington K, Olivier K, Thompson J, Vile RG. Expression of inflammatory chemokines combined with local tumor destruction enhances tumor regression and long-term immunity. Cancer Res. 2003;63(17):5505–12.

    CAS  PubMed  Google Scholar 

  104. Kajitani K, Tanaka Y, Arihiro K, Kataoka T, Ohdan H. Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells. Breast Cancer Res Treat. 2012;134(1):139–55.

    Article  PubMed  Google Scholar 

  105. Wendel M, Galani IE, Suri-Payer E, Cerwenka A. Natural killer cell accumulation in tumors is dependent on IFN-gamma and CXCR3 ligands. Cancer Res. 2008;68(20):8437–45.

    Article  CAS  PubMed  Google Scholar 

  106. Yu YR, Fong AM, Combadiere C, Gao JL, Murphy PM, Patel DD. Defective antitumor responses in CX3CR1-deficient mice. Int J Cancer. 2007;121(2):316–22.

    Article  CAS  PubMed  Google Scholar 

  107. Zhang X, Wei H, Wang H, Tian Z. Involvement of interaction between Fractalkine and CX3CR1 in cytotoxicity of natural killer cells against tumor cells. Oncol Rep. 2006;15(2):485–8.

    CAS  PubMed  Google Scholar 

  108. Maghazachi AA, Al-Aoukaty A, Schall TJ. CC chemokines induce the generation of killer cells from CD56+ cells. Eur J Immunol. 1996;26(2):315–9.

    Article  CAS  PubMed  Google Scholar 

  109. Taub DD, Sayers TJ, Carter CR, Ortaldo JR. Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis. J Immunol. 1995;155(8):3877–88.

    CAS  PubMed  Google Scholar 

  110. van den Berg A, Visser L, Poppema S. High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltrate in Hodgkin’s lymphoma. Am J Pathol. 1999;154(6):1685–91.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Iellem A, Colantonio L, D’Ambrosio D. Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells. Eur J Immunol. 2003;33(6):1488–96.

    Article  CAS  PubMed  Google Scholar 

  112. Gobert M, Treilleux I, Bendriss-Vermare N, Bachelot T, Goddard-Leon S, Arfi V, et al. Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Res. 2009;69(5):2000–9.

    Article  CAS  PubMed  Google Scholar 

  113. Wiedemann GM, Knott MM, Vetter VK, Rapp M, Haubner S, Fesseler J, et al. Cancer cell-derived IL-1alpha induces CCL22 and the recruitment of regulatory T cells. Oncoimmunology. 2016;5(9):e1175794.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Martinenaite E, Munir Ahmad S, Hansen M, Met O, Westergaard MW, Larsen SK, et al. CCL22-specific T cells: modulating the immunosuppressive tumor microenvironment. Oncoimmunology. 2016;5(11):e1238541.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Schutyser E, Struyf S, Proost P, Opdenakker G, Laureys G, Verhasselt B, et al. Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma. J Biol Chem. 2002;277(27):24584–93.

    Article  CAS  PubMed  Google Scholar 

  116. Bell D, Chomarat P, Broyles D, Netto G, Harb GM, Lebecque S, et al. In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med. 1999;190(10):1417–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Scarpino S, Stoppacciaro A, Ballerini F, Marchesi M, Prat M, Stella MC, et al. Papillary carcinoma of the thyroid: hepatocyte growth factor (HGF) stimulates tumor cells to release chemokines active in recruiting dendritic cells. Am J Pathol. 2000;156(3):831–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Mapara MY, Sykes M. Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. J Clin Oncol. 2004;22(6):1136–51.

    Article  CAS  PubMed  Google Scholar 

  119. Lesokhin AM, Hohl TM, Kitano S, Cortez C, Hirschhorn-Cymerman D, Avogadri F, et al. Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res. 2012;72(4):876–86.

    Article  CAS  PubMed  Google Scholar 

  120. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011;475(7355):222–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Loyher PL, Rochefort J, Baudesson de Chanville C, Hamon P, Lescaille G, Bertolus C, et al. CCR2 influences T regulatory cell migration to tumors and serves as a biomarker of cyclophosphamide sensitivity. Cancer Res. 2016;76(22):6483–94.

    Article  CAS  PubMed  Google Scholar 

  122. Fridlender ZG, Buchlis G, Kapoor V, Cheng G, Sun J, Singhal S, et al. CCL2 blockade augments cancer immunotherapy. Cancer Res. 2010;70(1):109–18.

    Article  CAS  PubMed  Google Scholar 

  123. Fridlender ZG, Kapoor V, Buchlis G, Cheng G, Sun J, Wang LC, et al. Monocyte chemoattractant protein-1 blockade inhibits lung cancer tumor growth by altering macrophage phenotype and activating CD8+ cells. Am J Respir Cell Mol Biol. 2011;44(2):230–7.

    Article  CAS  PubMed  Google Scholar 

  124. Tazzyman S, Niaz H, Murdoch C. Neutrophil-mediated tumour angiogenesis: subversion of immune responses to promote tumour growth. Semin Cancer Biol. 2013;23(3):149–58.

    Article  CAS  PubMed  Google Scholar 

  125. Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, et al. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995;270(45):27348–57.

    Article  CAS  PubMed  Google Scholar 

  126. Mohle R, Bautz F, Rafii S, Moore MA, Brugger W, Kanz L. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. Blood. 1998;91(12):4523–30.

    Article  CAS  PubMed  Google Scholar 

  127. Wong D, Korz W. Translating an antagonist of chemokine receptor CXCR4: from bench to bedside. Clin Cancer Res. 2008;14(24):7975–80.

    Article  CAS  PubMed  Google Scholar 

  128. Kozin SV, Kamoun WS, Huang Y, Dawson MR, Jain RK, Duda DG. Recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation. Cancer Res. 2010;70(14):5679–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Zheng K, Li HY, Su XL, Wang XY, Tian T, Li F, et al. Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells. J Exp Clin Cancer Res. 2010;29:31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Yeo EJ, Cassetta L, Qian BZ, Lewkowich I, Li JF, Stefater JA 3rd, et al. Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer Res. 2014;74(11):2962–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Welford AF, Biziato D, Coffelt SB, Nucera S, Fisher M, Pucci F, et al. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice. J Clin Invest. 2011;121(5):1969–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Hughes R, Qian BZ, Rowan C, Muthana M, Keklikoglou I, Olson OC, et al. Perivascular M2 macrophages stimulate tumor relapse after chemotherapy. Cancer Res. 2015;75(17):3479–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Qian BZ, Zhang H, Li J, He T, Yeo EJ, Soong DY, et al. FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis. J Exp Med. 2015;212(9):1433–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Jung K, Heishi T, Incio J, Huang Y, Beech EY, Pinter M, et al. Targeting CXCR4-dependent immunosuppressive Ly6C(low) monocytes improves antiangiogenic therapy in colorectal cancer. Proc Natl Acad Sci U S A. 2017;114(39):10455–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Strieter RM, Burdick MD, Mestas J, Gomperts B, Keane MP, Belperio JA. Cancer CXC chemokine networks and tumour angiogenesis. Eur J Cancer. 2006;42(6):768–78.

    Article  CAS  PubMed  Google Scholar 

  136. Romagnani P, Annunziato F, Lasagni L, Lazzeri E, Beltrame C, Francalanci M, et al. Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J Clin Invest. 2001;107(1):53–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Long H, Xie R, Xiang T, Zhao Z, Lin S, Liang Z, et al. Autocrine CCL5 signaling promotes invasion and migration of CD133+ ovarian cancer stem-like cells via NF-kappaB-mediated MMP-9 upregulation. Stem Cells. 2012;30(10):2309–19.

    Article  CAS  PubMed  Google Scholar 

  138. Swamydas M, Ricci K, Rego SL, Dreau D. Mesenchymal stem cell-derived CCL-9 and CCL-5 promote mammary tumor cell invasion and the activation of matrix metalloproteinases. Cell Adhes Migr. 2013;7(3):315.

    Article  Google Scholar 

  139. Johnson EL, Singh R, Singh S, Johnson-Holiday CM, Grizzle WE, Partridge EE, et al. CCL25-CCR9 interaction modulates ovarian cancer cell migration, metalloproteinase expression, and invasion. World J Surg Oncol. 2010;8:62.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Li J, Sun R, Tao K, Wang G. The CCL21/CCR7 pathway plays a key role in human colon cancer metastasis through regulation of matrix metalloproteinase-9. Dig Liver Dis. 2011;43(1):40–7.

    Article  PubMed  CAS  Google Scholar 

  141. Redondo-Munoz J, Jose Terol M, Garcia-Marco JA, Garcia-Pardo A. Matrix metalloproteinase-9 is up-regulated by CCL21/CCR7 interaction via extracellular signal-regulated kinase-1/2 signaling and is involved in CCL21-driven B-cell chronic lymphocytic leukemia cell invasion and migration. Blood. 2008;111(1):383–6.

    Article  CAS  PubMed  Google Scholar 

  142. Pan F, Ma S, Cao W, Liu H, Chen F, Chen X, et al. SDF-1alpha upregulation of MMP-2 is mediated by p38 MAPK signaling in pancreatic cancer cell lines. Mol Biol Rep. 2013;40(7):4139–46.

    Article  CAS  PubMed  Google Scholar 

  143. Peranzoni E, Rivas-Caicedo A, Bougherara H, Salmon H, Donnadieu E. Positive and negative influence of the matrix architecture on antitumor immune surveillance. Cell Mol Life Sci. 2013;70(23):4431–48.

    Article  CAS  PubMed  Google Scholar 

  144. Franco OE, Shaw AK, Strand DW, Hayward SW. Cancer associated fibroblasts in cancer pathogenesis. Semin Cell Dev Biol. 2010;21(1):33–9.

    Article  CAS  PubMed  Google Scholar 

  145. Borriello L, Nakata R, Sheard MA, Fernandez GE, Sposto R, Malvar J, et al. Cancer-associated fibroblasts share characteristics and protumorigenic activity with mesenchymal stromal cells. Cancer Res. 2017;77(18):5142–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Afik R, Zigmond E, Vugman M, Klepfish M, Shimshoni E, Pasmanik-Chor M, et al. Tumor macrophages are pivotal constructors of tumor collagenous matrix. J Exp Med. 2016;213(11):2315–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Sun X, Glynn DJ, Hodson LJ, Huo C, Britt K, Thompson EW, et al. CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model. Breast Cancer Res. 2017;19(1):4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Madsen DH, Jurgensen HJ, Siersbaek MS, Kuczek DE, Grey Cloud L, Liu S, et al. Tumor-associated macrophages derived from circulating inflammatory monocytes degrade collagen through cellular uptake. Cell Rep. 2017;21(13):3662–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Rovin BH, Lu L, Saxena R. A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun. 1999;259(2):344–8.

    Article  CAS  PubMed  Google Scholar 

  151. Rodero M, Rodero P, Descamps V, Lebbe C, Wolkenstein P, Aegerter P, et al. Melanoma susceptibility and progression: association study between polymorphisms of the chemokine (CCL2) and chemokine receptors (CX3CR1, CCR5). J Dermatol Sci. 2007;46(1):72–6.

    Article  CAS  PubMed  Google Scholar 

  152. Tse KP, Tsang NM, Chen KD, Li HP, Liang Y, Hsueh C, et al. MCP-1 promoter polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment. Clin Cancer Res. 2007;13(21):6320–6.

    Article  CAS  PubMed  Google Scholar 

  153. Liou JM, Lin JT, Huang SP, Wu CY, Wang HP, Lee YC, et al. RANTES-403 polymorphism is associated with reduced risk of gastric cancer in women. J Gastroenterol. 2008;43(2):115–23.

    Article  CAS  PubMed  Google Scholar 

  154. Duell EJ, Casella DP, Burk RD, Kelsey KT, Holly EA. Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma. Cancer Epidemiol Biomark Prev. 2006;15(4):726–31.

    Article  CAS  Google Scholar 

  155. Srivastava A, Pandey SN, Choudhuri G, Mittal B. CCR5 Delta32 polymorphism: associated with gallbladder cancer susceptibility. Scand J Immunol. 2008;67(5):516–22.

    Article  CAS  PubMed  Google Scholar 

  156. Ugurel S, Schrama D, Keller G, Schadendorf D, Brocker EB, Houben R, et al. Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol Immunother. 2008;57(5):685–91.

    Article  CAS  PubMed  Google Scholar 

  157. Huang Y, Chen H, Wang J, Bunjhoo H, Xiong W, Xu Y, et al. Relationship between CCR2-V64I polymorphism and cancer risk: a meta-analysis. Gene. 2013;524(1):54–8.

    Article  CAS  PubMed  Google Scholar 

  158. Wang J, Pan HF, Hu YT, Zhu Y, He Q. Polymorphism of IL-8 in 251 allele and gastric cancer susceptibility: a meta-analysis. Dig Dis Sci. 2010;55(7):1818–23.

    Article  CAS  PubMed  Google Scholar 

  159. Huang Q, Wang C, Qiu LJ, Shao F, Yu JH. IL-8-251A>T polymorphism is associated with breast cancer risk: a meta-analysis. J Cancer Res Clin Oncol. 2011;137(7):1147–50.

    Article  CAS  PubMed  Google Scholar 

  160. Wang N, Zhou R, Wang C, Guo X, Chen Z, Yang S, et al. -251 T/A polymorphism of the interleukin-8 gene and cancer risk: a HuGE review and meta-analysis based on 42 case-control studies. Mol Biol Rep. 2012;39(3):2831–41.

    Article  CAS  PubMed  Google Scholar 

  161. Gong H, Tan M, Wang Y, Shen B, Liu Z, Zhang F, et al. The CXCL12 G801A polymorphism and cancer risk: evidence from 17 case-control studies. Gene. 2012;509(2):228–31.

    Article  CAS  PubMed  Google Scholar 

  162. Ma XY, Jin Y, Sun HM, Yu L, Bai J, Chen F, et al. CXCL12 G801A polymorphism contributes to cancer susceptibility: a meta-analysis. Cell Mol Biol (Noisy-le-Grand). 2012;58(Suppl):OL1702–8.

    CAS  Google Scholar 

  163. Shen W, Cao X, Xi L, Deng L. CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis. Mol Biol Rep. 2012;39(2):2039–44.

    Article  CAS  PubMed  Google Scholar 

  164. Coniglio SJ, Eugenin E, Dobrenis K, Stanley ER, West BL, Symons MH, et al. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med. 2012;18:519–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Sauer M, Plutschow A, Jachimowicz RD, Kleefisch D, Reiners KS, Ponader S, et al. Baseline serum TARC levels predict therapy outcome in patients with Hodgkin lymphoma. Am J Hematol. 2013;88(2):113–5.

    Article  CAS  PubMed  Google Scholar 

  166. Cornforth AN, Lee GJ, Fowler AW, Carbonell DJ, Dillman RO. Increases in serum TARC/CCL17 levels are associated with progression-free survival in advanced melanoma patients in response to dendritic cell-based immunotherapy. J Clin Immunol. 2009;29(5):657–64.

    Article  CAS  PubMed  Google Scholar 

  167. Ansell SM, Maurer MJ, Ziesmer SC, Slager SL, Habermann TM, Link BK, et al. Elevated pretreatment serum levels of interferon-inducible protein-10 (CXCL10) predict disease relapse and prognosis in diffuse large B-cell lymphoma patients. Am J Hematol. 2012;87(9):865–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Lim SY, Yuzhalin AE, Gordon-Weeks AN, Muschel RJ. Targeting the CCL2-CCR2 signaling axis in cancer metastasis. Oncotarget. 2016;7(19):28697–710.

    Article  PubMed  PubMed Central  Google Scholar 

  169. Saji H, Koike M, Yamori T, Saji S, Seiki M, Matsushima K, et al. Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer. 2001;92(5):1085–91.

    Article  CAS  PubMed  Google Scholar 

  170. Valkovic T, Lucin K, Krstulja M, Dobi-Babic R, Jonjic N. Expression of monocyte chemotactic protein-1 in human invasive ductal breast cancer. Pathol Res Pract. 1998;194(5):335–40.

    Article  CAS  PubMed  Google Scholar 

  171. Zhang J, Patel L, Pienta KJ. Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of cancer molecular biology to the clinic. Prog Mol Biol Transl Sci. 2010;95:31–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Tsaur I, Noack A, Makarevic J, Oppermann E, Waaga-Gasser AM, Gasser M, et al. CCL2 chemokine as a potential biomarker for prostate cancer: a pilot study. Cancer Res Treat. 2015;47(2):306–12.

    Article  CAS  PubMed  Google Scholar 

  173. Carter PH, Brown GD, Cherney RJ, Batt DG, Chen J, Clark CM, et al. Discovery of a potent and orally bioavailable dual antagonist of CC chemokine receptors 2 and 5. ACS Med Chem Lett. 2015;6(4):439–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Doyon J, Coesemans E, Boeckx S, Buntinx M, Hermans B, Van Wauwe JP, et al. Discovery of potent, orally bioavailable small-molecule inhibitors of the human CCR2 receptor. ChemMedChem. 2008;3(4):660–9.

    Article  CAS  PubMed  Google Scholar 

  175. Zheng Y, Qin L, Zacarias NV, de Vries H, Han GW, Gustavsson M, et al. Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists. Nature. 2016;540(7633):458–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Berlato C, Khan MN, Schioppa T, Thompson R, Maniati E, Montfort A, et al. A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer. J Clin Invest. 2017;127(3):801–13.

    Article  PubMed  PubMed Central  Google Scholar 

  177. Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, et al. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci U S A. 2013;110(44):17945–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Sun W, Li WJ, Wei FQ, Wong TS, Lei WB, Zhu XL, et al. Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma. Oncotarget. 2016;7(25):37714–27.

    PubMed  PubMed Central  Google Scholar 

  179. Kurose K, Ohue Y, Wada H, Iida S, Ishida T, Kojima T, et al. Phase Ia study of FoxP3+ CD4 Treg depletion by infusion of a humanized anti-CCR4 antibody, KW-0761, in cancer patients. Clin Cancer Res. 2015;21(19):4327–36.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Neelam Malik for the editorial assistance. PL. L. was supported by ARC. This project has received funding from the European Union’s Seventh Programme for research, technological development, and demonstration under grant agreement no. 304810.

Author information

Authors and Affiliations

  1. Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses CIMI-Paris, Institut National de la, Santé et de la Recherche Médicale (INSERM), U1135, Centre National de la Recherche Scientifique (CNRS), ERL 8255, Institut Universitaire de Cancérologie (UPMC-IUC), CHU Pitié-Salpêtrière, Paris, France

    Pierre-Louis Loyher, Mathieu Paul Rodero, Christophe Combadière & Alexandre Boissonnas

Authors
  1. Pierre-Louis Loyher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mathieu Paul Rodero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christophe Combadière
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexandre Boissonnas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexandre Boissonnas .

Editor information

Editors and Affiliations

  1. Research Center for Immunodeficiencies, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Loyher, PL., Rodero, M.P., Combadière, C., Boissonnas, A. (2020). Role of Chemokines and Chemokine Receptors in Cancer. In: Rezaei, N. (eds) Cancer Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-30845-2_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-30845-2_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-30844-5

  • Online ISBN: 978-3-030-30845-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation