Skip to main content
SpringerLink
Log in

Role of the Immune Response in Disease Progression and Therapy in Multiple Myeloma

  • Chapter
  • First Online:
Plasma Cell Dyscrasias

Part of the book series: Cancer Treatment and Research ((CTAR,volume 169))

Abstract

Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells within the bone marrow. Unlike most solid tumors, which originate from epithelial cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage originating from a post-germinal B-cell. As such, the MM plasma cell represents an integral component of the immune system in terms of both antibody production and antigen presentation, albeit not efficiently. This fundamental difference has significant implications when one considers the implications of immunotherapy. In the case of lymphoid malignancies such as myeloma, immune-based strategies must take into consideration this important difference, potentially necessitating immunotherapy targeted toward MM to be altered from that targeted at solid tumors. Typically, the immune system “surveys” cells within our body and is able to recognize and attack cancerous cells that may arise. However, some cancer cells are able to evade immune surveillance and continue to flourish, causing disease. The major mechanism leading to an effective tumor-specific response is one that enables effective antigen processing and presentation with subsequent T-cell activation, expansion, and effective trafficking to the tumor site. Plasma cells employ several mechanisms to escape immune surveillance which include altered interactions with T-cells, DCs, bone marrow stromal cells (BMSC’s), and natural killer cells (NK Cells) that can be mediated by immunosuppressive cells such as and myeloid-derived suppressor cells (MDSC’s) and cytokines such as IL-10, TGFβ, and IL-6 as well as down-regulation of the antigen processing machinery. Many therapies have been developed to reestablish a functional immune system in MM patients. These include adoptive T-cell therapies to deliver more tumor-specific T-cells, vaccines to increase the tumor-specific precursor frequency of the endogenous T-cell population, immunomodulatory agents (IMiDs) such as thalidomide and lenalidomide to enhance global endogenous immunity, immunostimulatory cytokines, and antibodies to specifically target tumor-specific cell-surface proteins or cytokines. This review will dissect these various approaches currently being explored in MM as well as highlight some future directions for myeloma-specific immune-based strategies.

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 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. Alifano M et al (2014) Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer. PLoS ONE 9:e106914–11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Song G et al (2014) Effects of tumor microenvironment heterogeneity on nanoparticle disposition and efficacy in breast cancer tumor models. Clin Cancer Res 20:6083–6095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kumar V, Gabrilovich DI (2014) Hypoxia-inducible factors in regulation of immune responses in tumour microenvironment. Immunology 143:512–519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Manier S, Sacco A, Leleu X, Ghobrial IM, Roccaro AM (2012) Bone marrow microenvironment in multiple myeloma progression. J Biomed Biotechnol 2012:1–5

    Article  CAS  Google Scholar 

  5. Xu S et al (2012) Bone marrow-derived mesenchymal stromal cells are attracted by multiple myeloma cell-produced chemokine CCL25 and favor myeloma cell growth in vitro and in vivo. Stem Cells 30:266–279

    Article  CAS  PubMed  Google Scholar 

  6. Fulciniti M et al (2009) Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 114:371–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Spisek R et al (2007) Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy. J Exp Med 204:831–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bryant C et al (2013) Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg/Th17 balance. Blood Cancer J 3:e148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shen CJ, Yuan ZH, Liu YX, Hu GY (2012) Increased numbers of T helper 17 cells and the correlation with clinicopathological characteristics in multiple myeloma. J Int Med Res 40:556–564

    Article  CAS  PubMed  Google Scholar 

  10. Favaloro J et al (2014) Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma. Leuk Lymphoma 55:2893–2900

    Article  CAS  PubMed  Google Scholar 

  11. Zhou L et al (2007) IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8:967–974

    Article  CAS  PubMed  Google Scholar 

  12. Lichtenstein A, Berenson J, Norman D, Chang M-P, Charlie A (1989) Production of cytokines by bone marrow cells obtained from patients with multiple myeloma. Blood 74:1266–1273

    CAS  PubMed  Google Scholar 

  13. Noonan K et al (2010) A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood 116:3554–3563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 190:995–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kingsley CI, Karim M, Bushell AR, Wood KJ (2002) CD25+CD4+ regulatory T cells prevent graft rejection: CTLA-4- and IL-10-dependent immunoregulation of alloresponses. J Immunol 168:1080–1086

    Article  CAS  PubMed  Google Scholar 

  16. Ghiringhelli F (2005) CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-dependent manner. J Exp Med 202:1075–1085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Strauss L et al (2007) A unique subset of CD4+CD25highFoxp3+ T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res 13:4345–4354

    Article  CAS  PubMed  Google Scholar 

  18. Fahlen L (2005) T cells that cannot respond to TGF- escape control by CD4+CD25+ regulatory T cells. J Exp Med 201:737–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shull MM et al (1992) Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359:693–699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Muthu Raja KR et al (2012) Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma. PLoS ONE 7:e47077–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Giannopoulos K, Kaminska W, Hus I, Dmoszynska A (2012) The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterisation of immune status in multiple myeloma. Br J Cancer 106:546–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Prabhala RH (2006) Dysfunctional T regulatory cells in multiple myeloma. Blood 107:301–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Muthu Raja KR et al (2012) Functionally suppressive CD8 T regulatory cells are increased in patients with multiple myeloma: a cause for immune impairment. PLoS ONE 7:e49446–10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Ablamunits V, Bisikirska B, Herold KC (2010) Acquisition of regulatory function by human CD8(+) T cells treated with anti-CD3 antibody requires TNF. Eur J Immunol 40:2891–2901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Feyler S et al (2012) Tumour cell generation of inducible regulatory T-cells in multiple myeloma is contact-dependent and antigen-presenting cell-independent. PLoS ONE 7:e35981–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rueff J, Medinger M, Heim D, Passweg J, Stern M (2014) Lymphocyte subset recovery and outcome after autologous hematopoietic stem cell transplantation for plasma cell myeloma. Biol Blood Marrow Transplant 20:896–899

    Article  PubMed  Google Scholar 

  27. Benson DM et al (2010) The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood 116:2286–2294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Talebian L et al (2014) The natural killer-activating receptor, NKG2D, on CD3+CD8+ T cells plays a critical role in identifying and killing autologous myeloma cells. Transfusion 54:1515–1521

    Article  CAS  PubMed  Google Scholar 

  29. Jinushi M et al (2008) MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma. Proc Natl Acad Sci 105:1285–1290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pasiarski M, Grywalska E, Kosmaczewska A, Gozdz S, Rolinski J (2013) The frequency of myeloid and lymphoid dendritic cells in multiple myeloma patients is inversely correlated with disease progression. Potepy Hig Med Dosw 67:1–7

    Article  Google Scholar 

  31. Ratta M et al (2002) Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 100:230–237

    Article  CAS  PubMed  Google Scholar 

  32. Ramachandran IR et al (2013) Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow. J Immunol 190:3815–3823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Görgün GT et al (2013) Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans. Blood 121:2975–2987

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Serafini P et al (2006) Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 203:2691–2702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Noonan KA, Ghosh N, Rudraraju L, Bui M, Borrello I (2014) Targeting immune suppression with PDE5 inhibition in end-stage multiple myeloma. Cancer Immunol Res 2:725–731

    Article  PubMed  PubMed Central  Google Scholar 

  36. Borrello I et al (2000) Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte-macrophage colony-stimulating factor (GM-CSF)–producing tumor vaccines. Blood 95:3011–3019

    CAS  PubMed  Google Scholar 

  37. Gorin NC (2000) New developments in the therapy of acute myelocytic leukemia. Hematology 2000:69–89

    Article  Google Scholar 

  38. Gerull S et al (2013) Allo-SCT for multiple myeloma in the era of novel agents: a retrospective study on behalf of Swiss Blood SCT. Bone Marrow Transplant 48:408–413

    Article  CAS  PubMed  Google Scholar 

  39. Bjorkstrand BB et al (1996) Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood 88:4711–4718

    CAS  PubMed  Google Scholar 

  40. Gahrton G et al (1999) Syngeneic transplantation in multiple myeloma—a case-matched comparison with autologous and allogeneic transplantation. Bone Marrow Transplant 24:741–745

    Article  CAS  PubMed  Google Scholar 

  41. Barlogie B (2006) Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US intergroup trial S9321. J Clin Oncol 24:929–936

    Article  CAS  PubMed  Google Scholar 

  42. Kanakry CG et al (2014) Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS. Blood 124:3817–3827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mazo IB et al (2005) Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity 22:259–270

    Article  CAS  PubMed  Google Scholar 

  44. Di Rosa F, Pabst R (2005) The bone marrow: a nest for migratory memory T cells. Trends Immunol 26:360–366

    Article  PubMed  CAS  Google Scholar 

  45. Noonan K et al (2005) Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors. Cancer Res 65:2026–2034

    Article  CAS  PubMed  Google Scholar 

  46. Chu J et al (2014) CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia 28:917–927

    Article  CAS  PubMed  Google Scholar 

  47. Jiang H et al (2014) Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol 8:297–310

    Article  CAS  PubMed  Google Scholar 

  48. Meehan KR et al (2013) Adoptive cellular therapy using cells enriched for NKG2D+CD3+CD8+ T cells after autologous transplantation for myeloma. Biol Blood Marrow Transplant 19:129–137

    Article  PubMed  Google Scholar 

  49. Curti A et al (2007) Phase I/II clinical trial of sequential subcutaneous and intravenous delivery of dendritic cell vaccination for refractory multiple myeloma using patient-specific tumour idiotype protein or idiotype (VDJ)-derived class I-restricted peptides. Br J Haematol 139:415–424

    Article  CAS  PubMed  Google Scholar 

  50. Reichardt VL et al (1999) Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma—a feasibility study. Blood 93:2411–2419

    Google Scholar 

  51. Lim SH, Bailey-Wood R (1999) Idiotypic protein-pulsed dendritic cell vaccination in multiple myeloma. Int J Cancer 83:215–222

    Article  CAS  PubMed  Google Scholar 

  52. Yi Q, Desikan R, Barlogie B, Munshi N (2002) Optimizing dendritic cell-based immunotherapy in multiple myeloma. Br J Haematol 117:297–305

    Article  PubMed  Google Scholar 

  53. Rollig C et al (2011) Induction of cellular immune responses in patients with stage-I multiple myeloma after vaccination with autologous idiotype-pulsed dendritic cells. J Immunother 34:100–106

    Article  PubMed  CAS  Google Scholar 

  54. Hong S et al (2012) Optimizing dendritic cell vaccine for immunotherapy in multiple myeloma: tumour lysates are more potent tumour antigens than idiotype protein to promote anti-tumour immunity. Clin Exp Immunol 170:167–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rosenblatt J et al (2013) Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients. Clin Cancer Res 19:3640–3648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Schmitt M et al (2007) RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood 111:1357–1365

    Article  PubMed  CAS  Google Scholar 

  57. Greiner J et al (2010) High-dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Haematologica 95:1191–1197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Azuma T (2004) Myeloma cells are highly sensitive to the granule exocytosis pathway mediated by WT1-specific cytotoxic T lymphocytes. Clin Cancer Res 10:7402–7412

    Article  CAS  PubMed  Google Scholar 

  59. Tsuboi A et al (2007) Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma. Int J Hematol 86:414–417

    Article  PubMed  Google Scholar 

  60. Noonan K et al (2014) Lenalidomide immunomodulation with an allogeneic myeloma GVAX in a near complete remission induces durable clinical remissions. Blood 124:2137

    Google Scholar 

  61. Miguel JFS et al (1990) Immunophenotypic heterogeneity of multiple myeloma: influence on the biology and clinical course of the disease. Br J Haematol 77:185–190

    Article  Google Scholar 

  62. Matsui W et al (2004) Characterization of clonogenic multiple myeloma cells. Blood 103:2332–2336

    Article  CAS  PubMed  Google Scholar 

  63. Treon SP et al (2002) CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications. J Immunother 25:72–81

    Article  PubMed  Google Scholar 

  64. Zojer N, Kirchbacher K, Vesely M, Hübl W, Ludwig H (2006) Rituximab treatment provides no clinical benefit in patients with pretreated advanced multiple myeloma. Leuk Lymphoma 47:1103–1109

    Article  CAS  PubMed  Google Scholar 

  65. Moreau P et al (2007) Rituximab in CD20 positive multiple myeloma. Leukemia 1–2. doi:10.1038/sj.leu.2404558

    Google Scholar 

  66. Deaglio S (2006) In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia. Blood 108:1135–1144

    Article  CAS  PubMed  Google Scholar 

  67. van der Veer MS et al (2011) The therapeutic human CD38 antibody daratumumab improves the anti-myeloma effect of newly emerging multi-drug therapies. Blood Cancer J 1:e41–e43

    Article  PubMed  PubMed Central  Google Scholar 

  68. de Weers M et al (2011) Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 186:1840–1848

    Article  PubMed  CAS  Google Scholar 

  69. Jansen JHM et al (2012) Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking. Blood 120:2974

    Google Scholar 

  70. Overdijk MB et al (2012) Phagocytosis is a mechanism of action for daratumumab. Blood 120:4054

    Google Scholar 

  71. Plesner T et al (2012) Daratumumab, a CD38 monoclonal antibody in patients with multiple myeloma—data from a dose-escalation phase I/II study. Blood 120:73

    Article  CAS  Google Scholar 

  72. Plesner T et al (2013) Preliminary safety and efficacy data of daratumumab in combination with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma. Blood 122:1986

    Google Scholar 

  73. Deckert J et al (2014) SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin Cancer Res 20:4574–4583

    Article  CAS  PubMed  Google Scholar 

  74. Harada H et al (1993) Phenotypic difference of normal plasma cells from mature myeloma cells. Blood 81:2658–2663

    CAS  PubMed  Google Scholar 

  75. Chanan-Khan A et al (2010) Efficacy analysis from phase I study of Lorvotuzumab mertansine(IMGN901), used as monotherapy, in patients with heavily pre-treated CD56-positive multiple myeloma—a preliminary efficacy analysis. Blood 116:1962

    Google Scholar 

  76. Berdeja JG et al (2012) Phase i study of Lorvotuzumab mertansine (LM, IMGN901) in combination with Lenalidomide (Len) and Dexamethasone (Dex) in patients with CD56-positive relapsed or relapsed/refractory multiple myeloma (MM). Blood 120:4048

    Google Scholar 

  77. Kumaresan PR, Lai WC, Chuang SS, Bennett M, Mathew PA (2002) CS1, a novel member of the CD2 family, is homophilic and regulates NK cell function. Mol Immunol 39:1–8

    Article  CAS  PubMed  Google Scholar 

  78. Zonder JA et al (2012) A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood 120:552–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Jakubowiak AJ et al (2012) Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/refractory multiple myeloma. J Clin Oncol 30:1960–1965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lonial S et al (2012) Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 30:1953–1959

    Article  CAS  PubMed  Google Scholar 

  81. Hussein M et al (2010) A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma. Haematologica 95:845–848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Bensinger W et al (2012) A phase 1 study of lucatumumab, a fully human anti-CD40 antagonist monoclonal antibody administered intravenously to patients with relapsed or refractory multiple myeloma. Br J Haematol 159:58–66

    Article  CAS  PubMed  Google Scholar 

  83. Kurzrock R et al (2013) A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res 19:3659–3670

    Article  CAS  PubMed  Google Scholar 

  84. Voorhees PM et al (2013) A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. Br J Haematol 161:357–366

    Article  CAS  PubMed  Google Scholar 

  85. San-Miguel J et al (2014) Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma. Blood 123:4136–4142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Chapon M et al (2011) Progressive Upregulation of PD-1 in Primary and Metastatic Melanomas Associated with Blunted TCR Signaling in Infiltrating T Lymphocytes. Journal of Investigative Dermatology 131:1300–1307

    Article  CAS  PubMed  Google Scholar 

  87. Topalian SL, Drake CG, Pardoll DM (2012) Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 24:207–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yao S, Chen L (2013) Adaptive resistance: a tumor strategy to evade immune attack. Eur J Immunol 43:576–579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Iwai Y et al (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci 99:12293–12297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Topalian SL et al (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving Nivolumab. J Clin Oncol 32:1020–1030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Brahmer JR et al (2012) Safety and activity of anti–PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ansell SM et al (2015) PD-1 blockade with Nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319

    Article  PubMed  CAS  Google Scholar 

  93. Creelan BC (2014) Update on immune checkpoint inhibitors in lung cancer. Cancer Control 21:1–10

    Google Scholar 

  94. Lesokhin AM et al (2014) Preliminary results of a phase I study of Nivolumab (BMS-936558) in patients with relapsed or refractory lymphoid malignancies. Blood 124:291–291

    Google Scholar 

  95. Kearl TJ, Jing W, Gershan JA, Johnson BD (2013) Programmed death receptor-1/programmed death receptor ligand-1 blockade after transient lymphodepletion to treat myeloma. J Immunol 190:5620–5628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Schneider H et al (2006) Reversal of the TCR stop Signal by CTLA-4. Sci 313(5795):1972–5

    Google Scholar 

  97. Schmidt EM et al (2008) CTLA-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity. J Immunol 182:274–282

    Article  Google Scholar 

  98. Friedline RH et al (2009) CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance. J Exp Med 206:421–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Braga WMT, Vettore AL, Carvalho AC, Atanackovic D, Colleoni GWB (2011) Overexpression of CTLA-4 in the bone marrow of patients with multiple myeloma as a sign of local accumulation of immunosuppressive Tregs—perspectives for novel treatment strategies. Blood 118:1829

    Google Scholar 

  100. Hodi FS et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. De Keersmaecker B et al (2014) Immunomodulatory drugs improve the immune environment for dendritic cell-based immunotherapy in multiple myeloma patients after autologous stem cell transplantation. Cancer Immunol Immunother 63:1023–1036

    Article  PubMed  CAS  Google Scholar 

  102. Noonan K et al (2012) Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. Clin Cancer Res 18:1426–1434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Xu Y et al (2009) Immunomodulatory drugs reorganize cytoskeleton by modulating Rho GTPases. Blood 114:338–345

    Article  CAS  PubMed  Google Scholar 

  104. Henry JY et al (2013) Enhanced cross-priming of naive CD8+ T cells by dendritic cells treated by the IMiDs ®immunomodulatory compounds lenalidomide and pomalidomide. Immunology 139:377–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Clave E et al (2014) Lenalidomide consolidation and maintenance therapy after autologous stem cell transplant for multiple myeloma induces persistent changes in T-cell homeostasis. Leuk Lymphoma 55:1788–1795

    Article  CAS  PubMed  Google Scholar 

  106. Hayashi T et al (2005) Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br J Haematol 128:192–203

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, 21205, USA

    Susan J. Lee & Ivan Borrello

Authors
  1. Susan J. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivan Borrello
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivan Borrello .

Editor information

Editors and Affiliations

  1. Dept. of Medical Oncolgy/Hematology,, ASST-Spedali Civili di Brescia Dept. of Medical Oncolgy/Hematology,, Brescia, Brescia, Italy

    Aldo M. Roccaro

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Irene M. Ghobrial

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Lee, S.J., Borrello, I. (2016). Role of the Immune Response in Disease Progression and Therapy in Multiple Myeloma. In: Roccaro, A., Ghobrial, I. (eds) Plasma Cell Dyscrasias. Cancer Treatment and Research, vol 169. Springer, Cham. https://doi.org/10.1007/978-3-319-40320-5_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-40320-5_12

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-40318-2

  • Online ISBN: 978-3-319-40320-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation