The immune microenvironment of myeloma

Cancer Microenvironment

Volumn 4, Issue 3, 2011, Pages 313-323

  Noonan, Kimberly ^a   Borrello, Ivan ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

Bone marrow microenvironment; Immunology; Osteoclasts; T cells

Indexed keywords

CANCER VACCINE; CD11B ANTIGEN; CD56 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; DARATUMUMAB; DENOSUMAB; DEXAMETHASONE; HERMES ANTIGEN; INTERLEUKIN 17; INTERLEUKIN 23; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; LENALIDOMIDE; OSTEOCLAST DIFFERENTIATION FACTOR; PNEUMOCOCCUS VACCINE; POMALIDOMIDE; RITUXIMAB; SILDENAFIL; STROMAL CELL DERIVED FACTOR 1; SYNDECAN 1; TADALAFIL; THALIDOMIDE DERIVATIVE; TUMOR NECROSIS FACTOR ALPHA; VELTUZUMAB; VERY LATE ACTIVATION ANTIGEN 4; ZOLEDRONIC ACID;

ADIPOCYTE; ADOPTIVE TRANSFER; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIGEN EXPRESSION; AUTOLOGOUS BONE MARROW TRANSPLANTATION; B LYMPHOCYTE; BONE MARROW CELL; CANCER GROWTH; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CELL THERAPY; CELLULAR IMMUNITY; CHEMOTAXIS; COMPLEMENT DEPENDENT CYTOTOXICITY; CYTOKINE PRODUCTION; DENDRITIC CELL; DRUG POTENTIATION; DRUG RECEPTOR BINDING; ENZYME INHIBITION; EVENT FREE SURVIVAL; HUMAN; IMMUNE SYSTEM; IMMUNOMODULATION; LOW DRUG DOSE; MULTIPLE MYELOMA; NATURAL KILLER CELL; NATURAL KILLER T CELL; OSTEOBLAST; OSTEOCLAST; OVERALL SURVIVAL; PLASMA CELL; PRIORITY JOURNAL; REVIEW; STEM CELL; STROMA CELL; SUPPRESSOR CELL; T LYMPHOCYTE; TUMOR ESCAPE; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; UNSPECIFIED SIDE EFFECT;

EID: 84856485572     PISSN: 18752292     EISSN: 18752284     Source Type: Journal    
DOI: 10.1007/s12307-011-0086-3     Document Type: Review

References (122)

1. Mahindra A, Hideshima T, Anderson KC (2010) Multiple myeloma: biology of the disease. Blood Rev 24(Suppl 1):S5-11
2. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF et al (2002) A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 346(8):564-9 (Pubitemid 34438817)
3. Kyle RA, Rajkumar SV (2007) Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Hematol Oncol Clin North Am 21(6):1093-113, ix (Pubitemid 350051347)
4. Kyle RA, Rajkumar SV (2007) Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: emphasis on risk factors for progression. Br J Haematol 139 (5):730-43 (Pubitemid 350115735)
5. Spisek R, Kukreja A, Chen LC, Matthews P, Mazumder A, Vesole D et al (2007) Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy. J Exp Med 204(4):831-40, PMCID: 2118551 (Pubitemid 46631612)
6. Dhodapkar KM, Barbuto S, Matthews P, Kukreja A, Mazumder A, Vesole D et al (2008) Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma. Blood 112(7):2878-85, PMCID: 2556623
7. Gupta R, Ganeshan P, Hakim M, Verma R, Sharma A (2010) Kumar L. Significantly reduced regulatory T cell population in patients with untreated multiple myeloma, Leuk Res
8. Noonan K, Marchionni L, Anderson J, Pardoll D, Roodman GD, Borrello I (2010) A novel role of IL-17 producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood
9. von Lilienfeld-Toal M, Frank S, Leyendecker C, Feyler S, Jarmin S, Morgan R et al (2010) Reduced immune effector cell NKG2D expression and increased levels of soluble NKG2D ligands in multiple myeloma may not be causally linked. Cancer Immunol Immunother 59(6):829-39
10. Dhodapkar MV (2011) Richter J. Progress and challenges. Clin Immunol, Harnessing natural killer T (NKT) cells in human myeloma
11. Ratta M, Fagnoni F, Curti A, Vescovini R, Sansoni P, Oliviero B et al (2002) Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 100(1):230-7 (Pubitemid 35177452)
12. Shah N, Lonial S (2010) Evidence-based mini-review: treatment options for patients with relapsed/refractory myeloma previously treated with novel agents and high-dose chemotherapy and autologous stem-cell transplantation. Hematology Am Soc Hematol Educ Program 2010:310-3
13. Harousseau JL (2010) Multiple myeloma in the elderly: when to treat, when to go to transplant. Oncology (Williston Park) 24 (11):992-8
14. Kumar A, Galeb S, Djulbegovic B (2011) Treatment of patients with multiple myeloma: an overview of systematic reviews. Acta Haematol 125(1-2):8-22
15. Lacy MQ (2011) New immunomodulatory drugs in myeloma. Curr Hematol Malig Rep
16. Harousseau JL (2010) Ten years of improvement in the management of multiple myeloma: 2000-2010. Clin Lymphoma Myeloma Leuk 10(6):424-42
17. van de Donk NW, Lokhorst HM, Dimopoulos M, Cavo M, Morgan G, Einsele H et al (2011) Treatment of relapsed and refractory multiple myeloma in the era of novel agents. Cancer Treat Rev 37(4):266-83
18. Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W et al (2006) Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloidderived suppressor cell function. J Exp Med 203(12):2691-702, PMCID: 2118163 (Pubitemid 44833345)
19. Rollig C, Schmidt C, Bornhauser M, Ehninger G, Schmitz M, Auffermann-Gretzinger S (2011) Induction of cellular immune responses in patients with stage-I multiple myeloma after vaccination with autologous idiotype-pulsed dendritic cells. J Immunother 34(1):100-6
20. Yi Q, Szmania S, Freeman J, Qian J, Rosen NA, Viswamitra S et al (2010) Optimizing dendritic cell-based immunotherapy in multiple myeloma: intranodal injections of idiotype-pulsed CD40 ligand-matured vaccines led to induction of type-1 and cytotoxic T-cell immune responses in patients. Br J Haematol 150(5):554-64, PMCID: 2924470
21. Noonan K, Matsui W, Serafini P, Carbley R, Tan G, Khalili J et al (2005) Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors. Cancer Res 65(5):2026-34 (Pubitemid 40478633)
22. Barber A, Meehan KR, Sentman CL (2011) Treatment of multiple myeloma with adoptively transferred chimeric NKG2D receptor-expressing T cells. Gene Ther
23. Ocadlikova D, Kryukov F, Mollova K, Kovarova L, Buresdova I, Matejkova E et al (2010) Generation of myeloma-specific T cells using dendritic cells loaded with MUC1-and hTERT-drived nonapeptides or myeloma cell apoptotic bodies. Neoplasma 57 (5):455-64
24. Pilarski LM, Hipperson G, Seeberger K, Pruski E, Coupland RW, Belch AR (2000) Myeloma progenitors in the blood of patients with aggressive or minimal disease: engraftment and selfrenewal of primary human myeloma in the bone marrow of NOD SCID mice. Blood 95(3):1056-65 (Pubitemid 30062731)
25. Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y et al (2004) Characterization of clonogenic multiple myeloma cells. Blood 103(6):2332-6 (Pubitemid 38326254)
26. Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I et al (2008) Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res 68(1):190-7 (Pubitemid 351380120)
27. Yaccoby S, Barlogie B, Epstein J (1998) Primary myeloma cells growing in SCID-hu mice: a model for studying the biology and treatment of myeloma and its manifestations. Blood 92(8):2908-13 (Pubitemid 28469106)
28. Yaccoby S, Epstein J (1999) The proliferative potential of myeloma plasma cells manifest in the SCID-hu host. Blood 94 (10):3576-82 (Pubitemid 29536154)
29. Bakkus MH, Heirman C, Van Riet I, Van Camp B, Thielemans K (1992) Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation. Blood 80(9):2326-35
30. Taipale J, Beachy PA (2001) The Hedgehog and Wnt signalling pathways in cancer. Nature 411(6835):349-54 (Pubitemid 32467044)
31. Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Kim J et al (2007) Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA 104(10):4048-53, PMCID: 1805487
32. Agarwal JR, Matsui W (2010) Multiple myeloma: a paradigm for translation of the cancer stem cell hypothesis. Anticancer Agents Med Chem 10(2):116-20, PMCID: 3033115
33. Landgren O, Kyle RA, Rajkumar SV (2011) From myeloma precursor disease to multiple myeloma: new diagnostic concepts and opportunities for early intervention. Clin Cancer Res 17 (6):1243-52
34. Shapiro-Shelef M, Calame K (2005) Regulation of plasma-cell development. Nat Rev Immunol 5(3):230-42 (Pubitemid 40364824)
35. Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KG, Dorner T et al (2006) Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol 6(10):741-50 (Pubitemid 44453460)
36. Bergsagel PL, Kuehl WM (2005) Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol 23 (26):6333-8 (Pubitemid 46218843)
37. Teoh G, Anderson KC (1997) Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma. Hematol Oncol Clin North Am 11(1):27-42 (Pubitemid 27147744)
38. Uchiyama H, Barut BA, Mohrbacher AF, Chauhan D, Anderson KC (1993) Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood 82(12):3712-20 (Pubitemid 24006055)
39. Dhodapkar MV, Abe E, Theus A, Lacy M, Langford JK, Barlogie B et al (1998) Syndecan-1 is a multifunctional regulator of myeloma pathobiology: control of tumor cell survival, growth, and bone cell differentiation. Blood 91(8):2679-88 (Pubitemid 28227516)
40. Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS (1999) Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 93(5):1658-67 (Pubitemid 29102494)
41. Cao Y, Luetkens T, Kobold S, Hildebrandt Y, Gordic M, Lajmi N et al (2010) The cytokine/chemokine pattern in the bone marrow environment of multiple myeloma patients. Exp Hematol 38 (10):860-7
42. Medinger M, Fischer N, Tzankov A (2010) Vascular endothelial growth factor-related pathways in hemato-lymphoid malignancies. J Oncol 2010:729725, PMCID: 2875768
43. Lauta VM (2003) A review of the cytokine network in multiple myeloma: diagnostic, prognostic, and therapeutic implications. Cancer 97(10):2440-52 (Pubitemid 36542483)
44. Hwang W, Jung K, Jeon Y, Yun S, Kim TW, Choi I (2010) Knockdown of the interleukin-6 receptor alpha chain of dendritic cell vaccines enhances the therapeutic potential against IL-6 producing tumors. Vaccine 29(1):34-44
45. Chan KF, Siegel MR, Lenardo JM (2000) Signaling by the TNF receptor superfamily and T cell homeostasis. Immunity 13(4):419-22
46. Richardson P, Hideshima T, Anderson K (2002) Thalidomide: emerging role in cancer medicine. Annu Rev Med 53:629-57 (Pubitemid 34177899)
47. Sawamura M, Murakami H, Tsuchiya J (1996) Tumor necrosis factor-alpha and interleukin 4 in myeloma cell precursor differentiation. Leuk Lymphoma 21(1-2):31-6
48. Abildgaard N, Glerup H, Rungby J, Bendix-Hansen K, Kassem M, Brixen K et al (2000) Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma. Eur J Haematol 64(2):121-9 (Pubitemid 30167143)
49. Du J, Yuan Z, Zhang C, Fu W, Jiang H, Chen B et al (2010) Role of the TNF-alpha promoter polymorphisms for development of multiple myeloma and clinical outcome in thalidomide plus dexamethasone. Leuk Res 34(11):1453-8
50. Roodman GD (2010) Targeting the bone microenvironment in multiple myeloma. J Bone Miner Metab 28(3):244-50
51. Gunn WG, Conley A, Deininger L, Olson SD, Prockop DJ, Gregory CA (2006) A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: a potential role in the development of lytic bone disease and tumor progression in multiple myeloma. Stem Cells 24(4):986-91 (Pubitemid 44464731)
52. Choi SJ, Cruz JC, Craig F, Chung H, Devlin RD, Roodman GD et al (2000) Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood 96(2):671-5 (Pubitemid 30463390)
53. Giuliani N, Colla S, Rizzoli V (2004) New insight in the mechanism of osteoclast activation and formation in multiple myeloma: focus on the receptor activator of NF-kappaB ligand (RANKL). Exp Hematol 32(8):685-91 (Pubitemid 39092730)
54. Ehrlich LA, Roodman GD (2005) The role of immune cells and inflammatory cytokines in Paget's disease and multiple myeloma. Immunol Rev 208:252-66 (Pubitemid 41746397)
55. Sezer O, Heider U, Jakob C, Zavrski I, Eucker J, Possinger K et al (2002) Immunocytochemistry reveals RANKL expression of myeloma cells. Blood 99(12):4646-7, author reply 7 (Pubitemid 34627243)
56. Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J et al (2011) Randomized, double-blind study of denosumab versus zoledronic Acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 29(9):1125-32
57. Abe M, Hiura K, Wilde J, Shioyasono A, Moriyama K, Hashimoto T et al (2004) Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion. Blood 104 (8):2484-91 (Pubitemid 39331851)
58. Anderson KC, Jones RM, Morimoto C, Leavitt P, Barut BA (1989) Response patterns of purified myeloma cells to hematopoietic growth factors. Blood 73(7):1915-24 (Pubitemid 19145125)
59. Prabhala RH, Pelluru D, Fulciniti M, Prabhala HK, Nanjappa P, Song W et al (2010) Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 115(26):5385-92, PMCID: 2902136
60. Takahashi N, Mundy GR, Roodman GD (1986) Recombinant human interferon-gamma inhibits formation of human osteoclastlike cells. J Immunol 137(11):3544-9 (Pubitemid 17193314)
61. Abstracts of the American Society of Hematology 46th Annual Meeting. December 4-7, 2004, San Diego, California, USA. Blood. 2004;104(11 Pt 1):1a-1093a
62. Ehrlich LA, Chung HY, Ghobrial I, Choi SJ, Morandi F, Colla S et al (2005) IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood 106(4):1407-14 (Pubitemid 41129608)
63. Letsch A, Keilholz U, Assfalg G, Mailander V, Thiel E, Scheibenbogen C (2003) Bone marrow contains melanomareactive CD8+ effector T cells and, compared with peripheral blood, enriched numbers of melanoma-reactive CD8+ memory T cells. Cancer Res 63(17):5582-6 (Pubitemid 37139881)
64. Zhang X, Dong H, Lin W, Voss S, Hinkley L, Westergren M et al (2006) Human bone marrow: a reservoir for "enhanced effector memory" CD8+ T cells with potent recall function. J Immunol 177(10):6730-7 (Pubitemid 44715037)
65. Nitta H, Mihara K, Sakai A, Kimura A (2010) Expansion of CD8+/perforin+ effector memory T cells in the bone marrow of patients with thymoma-associated pure red cell aplasia. Br J Haematol 150(6):712-5
66. Dhodapkar MV, Krasovsky J, Olson K (2002) T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded dendritic cells. Proc Natl Acad Sci USA 99(20):13009-13, PMCID: 130577
67. Zou L, Barnett B, Safah H, Larussa VF, Evdemon-Hogan M, Mottram P et al (2004) Bone marrow is a reservoir for CD4 +CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res 64(22):8451-5 (Pubitemid 39491786)
68. Brimnes MK, Vangsted AJ, Knudsen LM, Gimsing P, Gang AO, Johnsen HE et al (2010) Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma. Scand J Immunol 72(6):540-7
69. Feyler S, von Lilienfeld-Toal M, Jarmin S, Marles L, Rawstron A, Ashcroft AJ et al (2009) CD4(+)CD25(+)FoxP3(+) regulatory T cells are increased whilst CD3(+)CD4(?)CD8(?)alphabetaTCR (+) Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden. Br J Haematol 144(5):686-95
70. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441 (7090):235-8
71. Korn T, Mitsdoerffer M, Croxford AL, Awasthi A, Dardalhon VA, Galileos G et al (2008) IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc Natl Acad Sci USA 105(47):18460-5, PMCID: 2587589
72. Jerud ES, Bricard G, Prorcelli SA (2006) CD1d-restricted natural killer T cells: roles in tumor immunosurveillance and tolerance. Transf Med Hemother 33(1):18-36
73. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L (2004) NKT cells: what's in a name? Nat Rev Immunol 4 (3):231-7 (Pubitemid 38339089)
74. Sun JC, Lopez-Verges S, Kim CC, DeRisi JL, Lanier LL (2011) NK cells and immune "memory". J Immunol 186(4):1891-7
75. Dhodapkar MV, Krasovsky J, Osman K, Geller MD (2003) Vigorous premalignancy-specific effector T cell response in the bone marrow of patients with monoclonal gammopathy. J Exp Med 198(11):1753-7 (Pubitemid 37494167)
76. Chang DH, Osman K, Connolly J, Kukreja A, Krasovsky J, Pack M et al (2005) Sustained expansion of NKT cells and antigenspecific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med 201(9):1503-17, PMCID: 1389847 (Pubitemid 40664093)
77. Gorgun G, Calabrese E, Soydan E, Hideshima T, Perrone G, Bandi M et al (2010) Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood 116(17):3227-37, PMCID: 2995353
78. Brown R, Murray A, Pope B, Sze DM, Gibson J, Ho PJ et al (2004) Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta in patients with myeloma. Br J Haematol 125(6):743-8 (Pubitemid 38813600)
79. Rosenblatt J, Vasir B, Uhl L, Blotta S, Macnamara C, Somaiya P et al (2011) Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma. Blood 117(2):393-402, PMCID: 3031474
80. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9 (3):162-74, PMCID: 2828349
81. Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP et al (2006) Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest 116(10):2777-90, PMCID: 1578632 (Pubitemid 44511641)
82. Mandruzzato S, Solito S, Falisi E, Francescato S, Chiarion-Sileni V, Mocellin S et al (2009) IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients. J Immunol 182 (10):6562-8
83. Serafini P, Borrello I, Bronte V (2006) Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol 16(1):53-65 (Pubitemid 43139709)
84. Medina MA, Quesada AR, Nunez de Castro I, Sanchez-Jimenez F (1999) Histamine, polyamines, and cancer. Biochem Pharmacol 57(12):1341-4 (Pubitemid 29225095)
85. Brito C, Naviliat M, Tiscornia AC, Vuillier F, Gualco G, Dighiero G et al (1999) Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death. J Immunol 162(6):3356-66 (Pubitemid 29313585)
86. Poschke I, Mougiakakos D, Hansson J, Masucci GV, Kiessling R (2010) Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer Res 70(11):4335-45
87. Schmielau J, Finn OJ (2001) Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res 61(12):4756-60 (Pubitemid 32691887)
88. Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J et al (2005) Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 65(8):3044-8 (Pubitemid 40524582)
89. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloidderived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49-59
90. Vuk-Pavlovic S, Bulur PA, Lin Y, Qin R, Szumlanski CL, Zhao X et al (2010) Immunosuppressive CD14+HLA-DRlow/-monocytes in prostate cancer. Prostate 70(4):443-455, PMCID: 2935631
91. Serafini P, Mgebroff S, Noonan K, Borrello I (2008) Myeloidderived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res 68 (13):5439-5449, PMCID: 2887390
92. Schilling T, Noth U, Klein-Hitpass L, Jakob F, Schutze N (2007) Plasticity in adipogenesis and osteogenesis of human mesenchymal stem cells. Mol Cell Endocrinol 271(1-2):1-17 (Pubitemid 46803047)
93. Tang CH, Lu DY, Yang RS, Tsai HY, Kao MC, Fu WM et al (2007) Leptin-induced IL-6 production is mediated by leptin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300 pathway in microglia. J Immunol 179(2):1292-1302
94. Mouzaki A, Panagoulias I, Dervilli Z, Zolota V, Spadidea P, Rodi M et al (2009) Expression patterns of leptin receptor (OB-R) isoforms and direct in vitro effects of recombinant leptin on OBR, leptin expression and cytokine secretion by human hematopoietic malignant cells. Cytokine 48(3):203-211
95. Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M (2005) Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol 174(11):6820-6828 (Pubitemid 40705645)
96. Mattioli B, Straface E, Matarrese P, Quaranta MG, Giordani L, Malorni W et al (2008) Leptin as an immunological adjuvant: enhanced migratory and CD8+ T cell stimulatory capacity of human dendritic cells exposed to leptin. FASEB J 22(6):2012-2022 (Pubitemid 351811477)
97. Robillard N, Avet-Loiseau H, Garand R, Moreau P, Pineau D, Rapp MJ et al (2003) CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma. Blood 102(3):1070-1071 (Pubitemid 36917806)
98. Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF et al (2009) Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst 101(4):248-255
99. Rossi EA, Rossi DL, Stein R, Goldenberg DM, Chang CH (2010) A bispecific antibody-IFNalpha2b immunocytokine targeting CD20 and HLA-DR is highly toxic to human lymphoma and multiple myeloma cells. Cancer Res 70(19):7600-7609
100. de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC et al (2011) Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 186 (3):1840-1848
101. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337-342 (Pubitemid 40852708)
102. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH et al (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354(8):821-831 (Pubitemid 43290920)
103. Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Smith J et al (2008) Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 26(30):4875-4882
104. Terpos E, Efstathiou E, Christoulas D, Roussou M, Katodritou E, Dimopoulos MA (2009) RANKL inhibition: clinical implications for the management of patients with multiple myeloma and solid tumors with bone metastases. Expert Opin Biol Ther 9 (4):465-479
105. Body JJ, Facon T, Coleman RE, Lipton A, Geurs F, Fan M et al (2006) A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 12(4):1221-1228 (Pubitemid 43342512)
106. Knight R (2005) IMiDs: a novel class of immunomodulators. Semin Oncol 32(4 Suppl 5):S24-S30 (Pubitemid 41111987)
107. Tageja N (2011) Lenalidomide-current understanding of mechanistic properties. Anticancer Agents Med Chem 11(3):315-326
108. Gandhi AK, Kang J, Capone L, Parton A, Wu L, Zhang LH et al (2010) Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomideinduced immunomodulation of T and NK cell function. Curr Cancer Drug Targets 10(2):155-167
109. Huang MC, Greig NH, Luo W, Tweedie D, Schwartz JB, Longo DL et al (2011) Preferential enhancement of older human T cell cytokine generation, chemotaxis, proliferation and survival by lenalidomide. Clin Immunol 138(2):201-211
110. Galustian C, Meyer B, Labarthe MC, Dredge K, Klaschka D, Henry J et al (2009) The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother 58(7):1033-1045
111. Noonan K, Ferguson A, Huff CA, Emerling A, Mgebroff S, Wilson R et al (2008) The immunomodulatory role of lenalidomide on Prevnar̊ responses in patients with relapsed multiple myeloma: a comprehensive analysis of the immune response. Blood (ASH Annual Meeting Abstracts) 112:2772
112. Dredge K, Marriott JB, Todryk SM, Muller GW, Chen R, Stirling DI et al (2002) Protective antitumor immunity induced by a costimulatory thalidomide analog in conjunction with whole tumor cell vaccination is mediated by increased Th1-type immunity. J Immunol 168(10):4914-4919 (Pubitemid 34495953)
113. Anderson G, Gries M, Kurihara N, Honjo T, Anderson J, Donnenberg V et al (2006) Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1. Blood 107(8):3098-3105
114. Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Fang HB, Cai L et al (2011) Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood 117(3):788-797, PMCID: 3035073
115. Siegel DS, Vij R, Vescio R, Borrello I, Martin TG, Berenson JR et al (2004) A phase I/II study of Xcellerated T cells after autologous peripheral blood stem cell transplantation in patients with multiple myeloma. Blood (ASH Annual Meeting Abstracts) 104:925
116. Zhang L, Kerkar SP, Yu Z, Zheng Z, Yang S, Restifo NP et al (2011) Improving Adoptive T Cell Therapy by Targeting and Controlling IL-12 Expression to the Tumor Environment. Mol Ther 19(4):751-759
117. Prieto PA, Durflinger KH, Wunderlich JR, Rosenberg SA, Dudley ME (2010) Enrichment of CD8+ cells from melanoma tumor-infiltrating lymphocyte cultures reveals tumor reactivity for use in adoptive cell therapy. J Immunother 33(5):547-556
118. Kuball J, de Boer K, Wagner E, Wattad M, Antunes E, Weeratna RD et al (2011) Pitfalls of vaccinations with WT1-, Proteinase3-and MUC1-derived peptides in combination with MontanideISA51 and CpG7909. Cancer Immunol Immunother 60(2):161-171, PMCID: 3024516
119. Maslak PG, Dao T, Krug LM, Chanel S, Korontsvit T, Zakhaleva Vet al (2010) Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia. Blood 116 (2):171-179, PMCID: 2910606
120. Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K et al (2010) Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci USA 107(31):13824-13829, PMCID: 2922237
121. Borrello I, Sotomayor EM, Rattis FM, Cooke SK, Gu L, Levitsky HI (2000) Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte-macrophage colonystimulating factor (GM-CSF)-producing tumor vaccines. Blood 95 (10):3011-3019 (Pubitemid 30321148)
122. Rapoport AP, Stadtmauer EA, Aqui N, Badros A, Cotte J, Chrisley L et al (2005) Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nat Med 11(11):1230-1237 (Pubitemid 43093671)