Tumor-induced myeloid dysfunction and its implications for cancer immunotherapy

Cancer Immunology, Immunotherapy

Volumn 64, Issue 1, 2015, Pages

  Messmer, Michelle N ^a   Netherby, Colleen S ^a   Banik, Debarati ^a   Abrams, Scott I ^a  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

Aberrant myelopoiesis; Cancer; IRF 8; MDSC

Indexed keywords

ANIMAL; BONE MARROW CELL; HUMAN; IMMUNOLOGY; IMMUNOTHERAPY; NEOPLASMS; PATHOLOGY; TUMOR ESCAPE;

ANIMALS; HUMANS; IMMUNOTHERAPY; MYELOID CELLS; NEOPLASMS; TUMOR ESCAPE;

EID: 84939121706     PISSN: 03407004     EISSN: 14320851     Source Type: Journal    
DOI: 10.1007/s00262-014-1639-3     Document Type: Review

References (125)

1. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013
2. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70
3. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12(4):253–268. doi:10.1038/nri3175
4. Ostrand-Rosenberg S, Sinha P, Beury DW, Clements VK (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22(4):275–281. doi:10.1016/j.semcancer.2012.01.011
5. Gabrilovich D (2004) Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 4(12):941–952. doi:10.1038/nri1498
6. Talmadge JE, Gabrilovich DI (2013) History of myeloid-derived suppressor cells. Nat Rev Cancer 13(10):739–752. doi:10.1038/nrc3581
7. Schafer M, Werner S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9(8):628–638. doi:10.1038/nrm2455
8. Shoenfeld Y, Tal A, Berliner S, Pinkhas J (1986) Leukocytosis in non hematological malignancies–a possible tumor-associated marker. J Cancer Res Clin Oncol 111(1):54–58
9. Dorn C, Bugl S, Malenke E, Muller MR, Weisel KC, Vogel U, Horger M, Kanz L, Kopp HG (2014) Paraneoplastic granulocyte colony-stimulating factor secretion in soft tissue sarcoma mimicking myeloproliferative neoplasia: a case report. BMC Res Notes 7:313. doi:10.1186/1756-0500-7-313
10. Schmidt H, Bastholt L, Geertsen P, Christensen IJ, Larsen S, Gehl J, von der Maase H (2005) Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. Br J Cancer 93(3):273–278. doi:10.1038/sj.bjc.6602702
11. Donskov F, von der Maase H (2006) Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J Clin Oncol 24(13):1997–2005. doi:10.1200/JCO.2005.03.9594
12. Paesmans M, Sculier JP, Lecomte J, Thiriaux J, Libert P, Sergysels R, Bureau G, Dabouis G, Van Cutsem O, Mommen P, Ninane V, Klastersky J (2000) Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer 89(3):523–533
13. Carus A, Ladekarl M, Hager H, Pilegaard H, Nielsen PS, Donskov F (2013) Tumor-associated neutrophils and macrophages in non-small cell lung cancer: no immediate impact on patient outcome. Lung Cancer 81(1):130–137. doi:10.1016/j.lungcan.2013.03.003
14. Lee Y, Kim SH, Han JY, Kim HT, Yun T, Lee JS (2012) Early neutrophil-to-lymphocyte ratio reduction as a surrogate marker of prognosis in never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. J Cancer Res Clin Oncol 138(12):2009–2016. doi:10.1007/s00432-012-1281-4
15. Chen MH, Chang PM, Chen PM, Tzeng CH, Chu PY, Chang SY, Yang MH (2009) Prognostic significance of a pretreatment hematologic profile in patients with head and neck cancer. J Cancer Res Clin Oncol 135(12):1783–1790. doi:10.1007/s00432-009-0625-1
16. Rudolph BM, Loquai C, Gerwe A, Bacher N, Steinbrink K, Grabbe S, Tuettenberg A (2014) Increased frequencies of CD11b(+) CD33(+) CD14(+) HLA-DR(low) myeloid-derived suppressor cells are an early event in melanoma patients. Exp Dermatol 23(3):202–204. doi:10.1111/exd.12336
17. Meyer C, Cagnon L, Costa-Nunes CM, Baumgaertner P, Montandon N, Leyvraz L, Michielin O, Romano E, Speiser DE (2014) Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother 63(3):247–257. doi:10.1007/s00262-013-1508-5
18. Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, Castelli C, Mariani L, Parmiani G, Rivoltini L (2007) Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol 25(18):2546–2553. doi:10.1200/JCO.2006.08.5829
19. −/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer Res 70(11):4335–4345. doi:10.1158/0008-5472.CAN-09-3767
20. + myeloid-derived suppressor cell expansion in cancer patients. J Immunol 182(10):6562–6568. doi:10.4049/jimmunol.0803831
21. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49–59. doi:10.1007/s00262-008-0523-4
22. Raychaudhuri B, Rayman P, Ireland J, Ko J, Rini B, Borden EC, Garcia J, Vogelbaum MA, Finke J (2011) Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma. Neuro Oncol 13(6):591–599. doi:10.1093/neuonc/nor042
23. Zhang H, Maric I, DiPrima MJ, Khan J, Orentas RJ, Kaplan RN, Mackall CL (2013) Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer. Blood 122(7):1105–1113. doi:10.1182/blood-2012-08-449413
24. Laborde RR, Lin Y, Gustafson MP, Bulur PA, Dietz AB (2014) Cancer vaccines in the world of immune suppressive monocytes (CD14(+)HLA-DR(lo/neg) Cells): the gateway to improved responses. Front Immunol 5:147. doi:10.3389/fimmu.2014.00147
25. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166(1):678–689
26. Brandau S, Trellakis S, Bruderek K, Schmaltz D, Steller G, Elian M, Suttmann H, Schenck M, Welling J, Zabel P, Lang S (2011) Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties. J Leukoc Biol 89(2):311–317. doi:10.1189/jlb.0310162
27. Vasquez-Dunddel D, Pan F, Zeng Q, Gorbounov M, Albesiano E, Fu J, Blosser RL, Tam AJ, Bruno T, Zhang H, Pardoll D, Kim Y (2013) STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients. J Clin Invest 123(4):1580–1589. doi:10.1172/JCI60083
28. − cells in squamous cell carcinoma of the head and neck. Cancer Sci 103(6):976–983. doi:10.1111/j.1349-7006.2012.02248.x
29. Sippel TR, White J, Nag K, Tsvankin V, Klaassen M, Kleinschmidt-DeMasters BK, Waziri A (2011) Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I. Clin Cancer Res 17(22):6992–7002. doi:10.1158/1078-0432.CCR-11-1107
30. Ohki S, Shibata M, Gonda K, Machida T, Shimura T, Nakamura I, Ohtake T, Koyama Y, Suzuki S, Ohto H, Takenoshita S (2012) Circulating myeloid-derived suppressor cells are increased and correlate to immune suppression, inflammation and hypoproteinemia in patients with cancer. Oncol Rep 28(2):453–458. doi:10.3892/or.2012.1812
31. Wu WC, Sun HW, Chen HT, Liang J, Yu XJ, Wu C, Wang Z, Zheng L (2014) Circulating hematopoietic stem and progenitor cells are myeloid-biased in cancer patients. Proc Natl Acad Sci USA 111(11):4221–4226. doi:10.1073/pnas.1320753111
32. Luger D, Yang YA, Raviv A, Weinberg D, Banerjee S, Lee MJ, Trepel J, Yang L, Wakefield LM (2013) Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects. PLoS One 8(10):e76115. doi:10.1371/journal.pone.0076115
33. Wang S, Fu Y, Ma K, Liu C, Jiao X, Du W, Zhang H, Wu X (2014) The significant increase and dynamic changes of the myeloid-derived suppressor cells percentage with chemotherapy in advanced NSCLC patients. Clin Transl Oncol 16(7):616–622. doi:10.1007/s12094-013-1125-y
34. Feng PH, Lee KY, Chang YL, Chan YF, Kuo LW, Lin TY, Chung FT, Kuo CS, Yu CT, Lin SM, Wang CH, Chou CL, Huang CD, Kuo HP (2012) CD14(+)S100A9(+) monocytic myeloid-derived suppressor cells and their clinical relevance in non-small cell lung cancer. Am J Respir Crit Care Med 186(10):1025–1036. doi:10.1164/rccm.201204-0636OC
35. Heuvers ME, Muskens F, Bezemer K, Lambers M, Dingemans AM, Groen HJ, Smit EF, Hoogsteden HC, Hegmans JP, Aerts JG (2013) Arginase-1 mRNA expression correlates with myeloid-derived suppressor cell levels in peripheral blood of NSCLC patients. Lung Cancer 81(3):468–474. doi:10.1016/j.lungcan.2013.06.005
36. + T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol 136(1):35–45. doi:10.1007/s00432-009-0634-0
37. Srivastava MK, Bosch JJ, Thompson JA, Ksander BR, Edelman MJ, Ostrand-Rosenberg S (2008) Lung cancer patients’ CD4(+) T cells are activated in vitro by MHC II cell-based vaccines despite the presence of myeloid-derived suppressor cells. Cancer Immunol Immunother 57(10):1493–1504. doi:10.1007/s00262-008-0490-9
38. Huang A, Zhang B, Wang B, Zhang F, Fan KX, Guo YJ (2013) Increased CD14(+)HLA-DR (−/low) myeloid-derived suppressor cells correlate with extrathoracic metastasis and poor response to chemotherapy in non-small cell lung cancer patients. Cancer Immunol Immunother 62(9):1439–1451. doi:10.1007/s00262-013-1450-6
39. Waight JD, Netherby C, Hensen ML, Miller A, Hu Q, Liu S, Bogner PN, Farren MR, Lee KP, Liu K, Abrams SI (2013) Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. J Clin Invest 123(10):4464–4478. doi:10.1172/JCI68189
40. Yu J, Du W, Yan F, Wang Y, Li H, Cao S, Yu W, Shen C, Liu J, Ren X (2013) Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J Immunol 190(7):3783–3797. doi:10.4049/jimmunol.1201449
41. +), myeloid-derived suppressor cells (MDSCs: monocytic, granulocytic) and polarised T helper cell profiles (Th1, Th2, Th17) in women with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC) and surgery: failure of abolition of abnormal treg profile with treatment and correlation of treg levels with pathological response to NAC. J Transl Med 11:16. doi:10.1186/1479-5876-11-16
42. Wald G, Barnes KT, Bing MT, Kresowik TP, Tomanek-Chalkley A, Kucaba TA, Griffith TS, Brown JA, Norian LA (2014) Minimal changes in the systemic immune response after nephrectomy of localized renal masses. Urol Oncol 32(5):589–600. doi:10.1016/j.urolonc.2014.01.023
43. Wang Z, Zhang Y, Liu Y, Wang L, Zhao L, Yang T, He C, Song Y, Gao Q (2014) Association of myeloid-derived suppressor cells and efficacy of cytokine-induced killer cell immunotherapy in metastatic renal cell carcinoma patients. J Immunother 37(1):43–50. doi:10.1097/CJI.0000000000000005
44. Kusmartsev S, Su Z, Heiser A, Dannull J, Eruslanov E, Kubler H, Yancey D, Dahm P, Vieweg J (2008) Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma. Clin Cancer Res 14(24):8270–8278. doi:10.1158/1078-0432.CCR-08-0165
45. Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich PY, Mendrzyk R, Hilf N, Schoor O, Fritsche J, Mahr A, Maurer D, Vass V, Trautwein C, Lewandrowski P, Flohr C, Pohla H, Stanczak JJ, Bronte V, Mandruzzato S, Biedermann T, Pawelec G, Derhovanessian E, Yamagishi H, Miki T, Hongo F, Takaha N, Hirakawa K, Tanaka H, Stevanovic S, Frisch J, Mayer-Mokler A, Kirner A, Rammensee HG, Reinhardt C, Singh-Jasuja H (2012) Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med 18(8):1254–1261. doi:10.1038/nm.2883
46. Brusa D, Simone M, Gontero P, Spadi R, Racca P, Micari J, Degiuli M, Carletto S, Tizzani A, Matera L (2013) Circulating immunosuppressive cells of prostate cancer patients before and after radical prostatectomy: profile comparison. Int J Urol 20(10):971–978. doi:10.1111/iju.12086
47. Idorn M, Kollgaard T, Kongsted P, Sengelov L, Thor Straten P (2014) Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer. Cancer Immunol Immunother 63(11):1177–1187. doi:10.1007/s00262-014-1591-2
48. Hoechst B, Ormandy LA, Ballmaier M, Lehner F, Kruger C, Manns MP, Greten TF, Korangy F (2008) A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells. Gastroenterology 135(1):234–243. doi:10.1053/j.gastro.2008.03.020
49. Shen P, Wang A, He M, Wang Q, Zheng S (2014) Increased circulating Lin(-/low) CD33(+) HLA-DR(−) myeloid-derived suppressor cells in hepatocellular carcinoma patients. Hepatol Res 44(6):639–650. doi:10.1111/hepr.12167
50. Yazawa T, Shibata M, Gonda K, Machida T, Suzuki S, Kenjo A, Nakamura I, Tsuchiya T, Koyama Y, Sakurai K, Shimura T, Tomita R, Ohto H, Gotoh M, Takenoshita S (2013) Increased IL-17 production correlates with immunosuppression involving myeloid-derived suppressor cells and nutritional impairment in patients with various gastrointestinal cancers. Mol Clin Oncol 1(4):675–679. doi:10.3892/mco.2013.134
51. Gao J, Wu Y, Su Z, Amoah Barnie P, Jiao Z, Bie Q, Lu L, Wang S, Xu H (2014) Infiltration of alternatively activated macrophages in cancer tissue is associated with MDSC and Th2 polarization in patients with esophageal cancer. PLoS One 9(8):e104453. doi:10.1371/journal.pone.0104453
52. Wang L, Chang EW, Wong SC, Ong SM, Chong DQ, Ling KL (2013) Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. J Immunol 190(2):794–804. doi:10.4049/jimmunol.1202088
53. Khaled YS, Ammori BJ, Elkord E (2014) Increased levels of granulocytic myeloid-derived suppressor cells in peripheral blood and tumour tissue of pancreatic cancer patients. J Immunol Res 2014:879897. doi:10.1155/2014/879897
54. Bazhin AV, Shevchenko I, Umansky V, Werner J, Karakhanova S (2014) Two immune faces of pancreatic adenocarcinoma: possible implication for immunotherapy. Cancer Immunol Immunother 63(1):59–65. doi:10.1007/s00262-013-1485-8
55. Zhang B, Wang Z, Wu L, Zhang M, Li W, Ding J, Zhu J, Wei H, Zhao K (2013) Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS One 8(2):e57114. doi:10.1371/journal.pone.0057114
56. Romano A, Conticello C, Cavalli M, Vetro C, La Fauci A, Parrinello NL, Di Raimondo F (2014) Immunological dysregulation in multiple myeloma microenvironment. Biomed Res Int 2014:198539. doi:10.1155/2014/198539
57. von Hohenstaufen KA, Conconi A, de Campos CP, Franceschetti S, Bertoni F, Margiotta Casaluci G, Stathis A, Ghielmini M, Stussi G, Cavalli F, Gaidano G, Zucca E (2013) Prognostic impact of monocyte count at presentation in mantle cell lymphoma. Br J Haematol 162(4):465–473. doi:10.1111/bjh.12409
58. Giallongo C, Parrinello N, Tibullo D, La Cava P, Romano A, Chiarenza A, Barbagallo I, Palumbo GA, Stagno F, Vigneri P, Di Raimondo F (2014) Myeloid derived suppressor cells (MDSCs) are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs) in chronic myeloid leukemia patients. PLoS One 9(7):e101848. doi:10.1371/journal.pone.0101848
59. Christiansson L, Soderlund S, Svensson E, Mustjoki S, Bengtsson M, Simonsson B, Olsson-Stromberg U, Loskog AS (2013) Increased level of myeloid-derived suppressor cells, programmed death receptor ligand 1/programmed death receptor 1, and soluble CD25 in Sokal high risk chronic myeloid leukemia. PLoS One 8(1):e55818. doi:10.1371/journal.pone.0055818
60. Solito S, Marigo I, Pinton L, Damuzzo V, Mandruzzato S, Bronte V (2014) Myeloid-derived suppressor cell heterogeneity in human cancers. Ann N Y Acad Sci 1319:47–65. doi:10.1111/nyas.12469
61. Pak AS, Wright MA, Matthews JP, Collins SL, Petruzzelli GJ, Young MR (1995) Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin Cancer Res 1(1):95–103
62. Duechler M, Peczek L, Zuk K, Zalesna I, Jeziorski A, Czyz M (2014) The heterogeneous immune microenvironment in breast cancer is affected by hypoxia-related genes. Immunobiology 219(2):158–165. doi:10.1016/j.imbio.2013.09.003
63. Achberger S, Aldrich W, Tubbs R, Crabb JW, Singh AD, Triozzi PL (2014) Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease. Mol Immunol 58(2):182–186. doi:10.1016/j.molimm.2013.11.018
64. Finkelstein SE, Carey T, Fricke I, Yu D, Goetz D, Gratz M, Dunn M, Urbas P, Daud A, DeConti R, Antonia S, Gabrilovich D, Fishman M (2010) Changes in dendritic cell phenotype after a new high-dose weekly schedule of interleukin-2 therapy for kidney cancer and melanoma. J Immunother 33(8):817–827. doi:10.1097/CJI.0b013e3181ecccad
65. Weide B, Martens A, Zelba H, Stutz C, Derhovanessian E, Di Giacomo AM, Maio M, Sucker A, Schilling B, Schadendorf D, Buttner P, Garbe C, Pawelec G (2014) Myeloid-derived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1- or melan-A-specific T cells. Clin Cancer Res 20(6):1601–1609. doi:10.1158/1078-0432.CCR-13-2508
66. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174. doi:10.1038/nri2506
67. Verschoor CP, Johnstone J, Millar J, Dorrington MG, Habibagahi M, Lelic A, Loeb M, Bramson JL, Bowdish DM (2013) Blood CD33(+)HLA-DR(−) myeloid-derived suppressor cells are increased with age and a history of cancer. J Leukoc Biol 93(4):633–637. doi:10.1189/jlb.0912461
68. Rosmarin AG, Yang Z, Resendes KK (2005) Transcriptional regulation in myelopoiesis: hematopoietic fate choice, myeloid differentiation, and leukemogenesis. Exp Hematol 33(2):131–143. doi:10.1016/j.exphem.2004.08.015
69. Zhu J, Emerson SG (2002) Hematopoietic cytokines, transcription factors and lineage commitment. Oncogene 21(21):3295–3313. doi:10.1038/sj.onc.1205318
70. Friedman AD (2002) Transcriptional regulation of granulocyte and monocyte development. Oncogene 21(21):3377–3390. doi:10.1038/sj.onc.1205324
71. Iwasaki H, Akashi K (2007) Myeloid lineage commitment from the hematopoietic stem cell. Immunity 26(6):726–740. doi:10.1016/j.immuni.2007.06.004
72. Nagai Y, Garrett KP, Ohta S, Bahrun U, Kouro T, Akira S, Takatsu K, Kincade PW (2006) Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity 24(6):801–812. doi:10.1016/j.immuni.2006.04.008
73. King KY, Goodell MA (2011) Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol 11(10):685–692. doi:10.1038/nri3062
74. Vahedi G, Poholek AC, Hand TW, Laurence A, Kanno Y, O’Shea JJ, Hirahara K (2013) Helper T-cell identity and evolution of differential transcriptomes and epigenomes. Immunol Rev 252(1):24–40. doi:10.1111/imr.12037
75. Schiavoni G, Mattei F, Sestili P, Borghi P, Venditti M, Morse HC 3rd, Belardelli F, Gabriele L (2002) ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells. J Exp Med 196(11):1415–1425
76. Tailor P, Tamura T, Kong HJ, Kubota T, Kubota M, Borghi P, Gabriele L, Ozato K (2007) The feedback phase of type I interferon induction in dendritic cells requires interferon regulatory factor 8. Immunity 27(2):228–239. doi:10.1016/j.immuni.2007.06.009
77. Gabriele L, Ozato K (2007) The role of the interferon regulatory factor (IRF) family in dendritic cell development and function. Cytokine Growth Factor Rev 18(5–6):503–510. doi:10.1016/j.cytogfr.2007.06.008
78. Tamura T, Tailor P, Yamaoka K, Kong HJ, Tsujimura H, O’Shea JJ, Singh H, Ozato K (2005) IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. J Immunol 174(5):2573–2581
79. Holtschke T, Lohler J, Kanno Y, Fehr T, Giese N, Rosenbauer F, Lou J, Knobeloch KP, Gabriele L, Waring JF, Bachmann MF, Zinkernagel RM, Morse HC 3rd, Ozato K, Horak I (1996) Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell 87(2):307–317
80. Scheller M, Foerster J, Heyworth CM, Waring JF, Lohler J, Gilmore GL, Shadduck RK, Dexter TM, Horak I (1999) Altered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein. Blood 94(11):3764–3771
81. Tsujimura H, Tamura T, Ozato K (2003) Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-producing plasmacytoid dendritic cells. J Immunol 170(3):1131–1135
82. Schiavoni G, Mattei F, Borghi P, Sestili P, Venditti M, Morse HC 3rd, Belardelli F, Gabriele L (2004) ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood 103(6):2221–2228. doi:10.1182/blood-2003-09-3007
83. Scharton-Kersten T, Contursi C, Masumi A, Sher A, Ozato K (1997) Interferon consensus sequence binding protein-deficient mice display impaired resistance to intracellular infection due to a primary defect in interleukin 12 p40 induction. J Exp Med 186(9):1523–1534
84. Fehr T, Schoedon G, Odermatt B, Holtschke T, Schneemann M, Bachmann MF, Mak TW, Horak I, Zinkernagel RM (1997) Crucial role of interferon consensus sequence binding protein, but neither of interferon regulatory factor 1 nor of nitric oxide synthesis for protection against murine listeriosis. J Exp Med 185(5):921–931
85. Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S, Azevedo J, Fortin A, Haniffa M, Ceron-Gutierrez L, Bacon CM, Menon G, Trouillet C, McDonald D, Carey P, Ginhoux F, Alsina L, Zumwalt TJ, Kong XF, Kumararatne D, Butler K, Hubeau M, Feinberg J, Al-Muhsen S, Cant A, Abel L, Chaussabel D, Doffinger R, Talesnik E, Grumach A, Duarte A, Abarca K, Moraes-Vasconcelos D, Burk D, Berghuis A, Geissmann F, Collin M, Casanova JL, Gros P (2011) IRF8 mutations and human dendritic-cell immunodeficiency. N Engl J Med 365(2):127–138. doi:10.1056/NEJMoa1100066
86. Tamura T, Thotakura P, Tanaka TS, Ko MS, Ozato K (2005) Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. Blood 106(6):1938–1947. doi:10.1182/blood-2005-01-0080
87. Dror N, Alter-Koltunoff M, Azriel A, Amariglio N, Jacob-Hirsch J, Zeligson S, Morgenstern A, Tamura T, Hauser H, Rechavi G, Ozato K, Levi BZ (2007) Identification of IRF-8 and IRF-1 target genes in activated macrophages. Mol Immunol 44(4):338–346. doi:10.1016/j.molimm.2006.02.026
88. Wang IM, Contursi C, Masumi A, Ma X, Trinchieri G, Ozato K (2000) An IFN-gamma-inducible transcription factor, IFN consensus sequence binding protein (ICSBP), stimulates IL-12 p40 expression in macrophages. J Immunol 165(1):271–279
89. Giese NA, Gabriele L, Doherty TM, Klinman DM, Tadesse-Heath L, Contursi C, Epstein SL, Morse HC 3rd (1997) Interferon (IFN) consensus sequence-binding protein, a transcription factor of the IFN regulatory factor family, regulates immune responses in vivo through control of interleukin 12 expression. J Exp Med 186(9):1535–1546
90. Liu J, Ma X (2006) Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-kappaB, and PU.1. J Biol Chem 281(28):19188–19195. doi:10.1074/jbc.M602059200
91. Mullins DW, Martins RS, Elgert KD (2003) Tumor-derived cytokines dysregulate macrophage interferon-gamma responsiveness and interferon regulatory factor-8 expression. Exp Biol Med (Maywood) 228(3):270–277
92. Tamura T, Yanai H, Savitsky D, Taniguchi T (2008) The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 26:535–584. doi:10.1146/annurev.immunol.26.021607.090400
93. Driggers PH, Ennist DL, Gleason SL, Mak WH, Marks MS, Levi BZ, Flanagan JR, Appella E, Ozato K (1990) An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. Proc Natl Acad Sci U S A 87(10):3743–3747
94. Kanno Y, Kozak CA, Schindler C, Driggers PH, Ennist DL, Gleason SL, Darnell JE Jr, Ozato K (1993) The genomic structure of the murine ICSBP gene reveals the presence of the gamma interferon-responsive element, to which an ISGF3 alpha subunit (or similar) molecule binds. Mol Cell Biol 13(7):3951–3963
95. Nguyen H, Hiscott J, Pitha PM (1997) The growing family of interferon regulatory factors. Cytokine Growth Factor Rev 8(4):293–312
96. Tamura T, Ozato K (2002) ICSBP/IRF-8: its regulatory roles in the development of myeloid cells. J Interferon Cytokine Res 22(1):145–152. doi:10.1089/107999002753452755
97. Politis AD, Ozato K, Coligan JE, Vogel SN (1994) Regulation of IFN-gamma-induced nuclear expression of IFN consensus sequence binding protein in murine peritoneal macrophages. J Immunol 152(5):2270–2278
98. Zhao J, Kong HJ, Li H, Huang B, Yang M, Zhu C, Bogunovic M, Zheng F, Mayer L, Ozato K, Unkeless J, Xiong H (2006) IRF-8/interferon (IFN) consensus sequence-binding protein is involved in Toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways. J Biol Chem 281(15):10073–10080. doi:10.1074/jbc.M507788200
99. Weisz A, Marx P, Sharf R, Appella E, Driggers PH, Ozato K, Levi BZ (1992) Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. J Biol Chem 267(35):25589–25596
100. Schmidt M, Nagel S, Proba J, Thiede C, Ritter M, Waring JF, Rosenbauer F, Huhn D, Wittig B, Horak I, Neubauer A (1998) Lack of interferon consensus sequence binding protein (ICSBP) transcripts in human myeloid leukemias. Blood 91(1):22–29
101. Marigo I, Bosio E, Solito S, Mesa C, Fernandez A, Dolcetti L, Ugel S, Sonda N, Bicciato S, Falisi E, Calabrese F, Basso G, Zanovello P, Cozzi E, Mandruzzato S, Bronte V (2010) Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity 32(6):790–802. doi:10.1016/j.immuni.2010.05.010
102. Thevenot PT, Sierra RA, Raber PL, Al-Khami AA, Trillo-Tinoco J, Zarreii P, Ochoa AC, Cui Y, Del Valle L, Rodriguez PC (2014) The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. Immunity 41(3):389–401. doi:10.1016/j.immuni.2014.08.015
103. Zhang W, Pal SK, Liu X, Yang C, Allahabadi S, Bhanji S, Figlin RA, Yu H, Reckamp KL (2013) Myeloid clusters are associated with a pro-metastatic environment and poor prognosis in smoking-related early stage non-small cell lung cancer. PLoS One 8(5):e65121. doi:10.1371/journal.pone.0065121
104. Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, Sedrak C, Jungbluth AA, Chua R, Yang AS, Roman RA, Rosner S, Benson B, Allison JP, Lesokhin AM, Gnjatic S, Wolchok JD (2012) Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 366(10):925–931. doi:10.1056/NEJMoa1112824
105. Chen G, Emens LA (2013) Chemoimmunotherapy: reengineering tumor immunity. Cancer Immunol Immunother 62(2):203–216. doi:10.1007/s00262-012-1388-0
106. James BR, Anderson KG, Brincks EL, Kucaba TA, Norian LA, Masopust D, Griffith TS (2014) CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma. Cancer Immunol Immunother 63(11):1213–1227. doi:10.1007/s00262-014-1598-8
107. Bronte V, Serafini P, Apolloni E, Zanovello P (2001) Tumor-induced immune dysfunctions caused by myeloid suppressor cells. J Immunother 24(6):431–446
108. Qin H, Lerman B, Sakamaki I, Wei G, Cha SC, Rao SS, Qian J, Hailemichael Y, Nurieva R, Dwyer KC, Roth J, Yi Q, Overwijk WW, Kwak LW (2014) Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice. Nat Med 20(6):676–681. doi:10.1038/nm.3560
109. Shojaei F, Wu X, Qu X, Kowanetz M, Yu L, Tan M, Meng YG, Ferrara N (2009) G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci U S A 106(16):6742–6747. doi:10.1073/pnas.0902280106
110. Waight JD, Hu Q, Miller A, Liu S, Abrams SI (2011) Tumor-derived G-CSF facilitates neoplastic growth through a granulocytic myeloid-derived suppressor cell-dependent mechanism. PLoS One 6(11):e27690. doi:10.1371/journal.pone.0027690
111. Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ, Vonderheide RH (2012) Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21(6):822–835. doi:10.1016/j.ccr.2012.04.025
112. Reeves G (2014) Overview of use of G-CSF and GM-CSF in the treatment of acute radiation injury. Health Phys 106(6):699–703. doi:10.1097/HP.0000000000000090
113. Kaufman HL, Ruby CE, Hughes T, Slingluff CL Jr (2014) Current status of granulocyte-macrophage colony-stimulating factor in the immunotherapy of melanoma. J Immunother Cancer 2:11. doi:10.1186/2051-1426-2-11
114. Nutt SL, Morrison AM, Dorfler P, Rolink A, Busslinger M (1998) Identification of BSAP (Pax-5) target genes in early B-cell development by loss- and gain-of-function experiments. EMBO J 17(8):2319–2333. doi:10.1093/emboj/17.8.2319
115. Dimberg A, Karehed K, Nilsson K, Oberg F (2006) Inhibition of monocytic differentiation by phosphorylation-deficient Stat1 is associated with impaired expression of Stat2, ICSBP/IRF8 and C/EBPepsilon. Scand J Immunol 64(3):271–279. doi:10.1111/j.1365-3083.2006.01827.x
116. Iclozan C, Antonia S, Chiappori A, Chen DT, Gabrilovich D (2013) Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer. Cancer Immunol Immunother 62(5):909–918. doi:10.1007/s00262-013-1396-8
117. Couzin-Frankel J (2013) Breakthrough of the year 2013. Cancer immunotherapy. Science 342(6165):1432–1433. doi:10.1126/science.342.6165.1432
118. Rolinski J, Hus I (2014) Breaking immunotolerance of tumors: a new perspective for dendritic cell therapy. J Immunotoxicol 11(4):311–318. doi:10.3109/1547691X.2013.865094
119. Jochems C, Tucker JA, Tsang KY, Madan RA, Dahut WL, Liewehr DJ, Steinberg SM, Gulley JL, Schlom J (2014) A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates. Cancer Immunol Immunother 63(4):407–418. doi:10.1007/s00262-014-1524-0
120. Tarhini AA, Butterfield LH, Shuai Y, Gooding WE, Kalinski P, Kirkwood JM (2012) Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-CTLA4 antibody and interferon-alpha or TLR-9 agonist and GM-CSF with peptide vaccination. J Immunother 35(9):702–710. doi:10.1097/CJI.0b013e318272569b
121. Tarhini AA, Edington H, Butterfield LH, Lin Y, Shuai Y, Tawbi H, Sander C, Yin Y, Holtzman M, Johnson J, Rao UN, Kirkwood JM (2014) Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab. PLoS One 9(2):e87705. doi:10.1371/journal.pone.0087705
122. Wu P, Wu D, Ni C, Ye J, Chen W, Hu G, Wang Z, Wang C, Zhang Z, Xia W, Chen Z, Wang K, Zhang T, Xu J, Han Y, Zhang T, Wu X, Wang J, Gong W, Zheng S, Qiu F, Yan J, Huang J (2014) gammadeltaT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity 40(5):785–800. doi:10.1016/j.immuni.2014.03.013
123. Annels NE, Shaw VE, Gabitass RF, Billingham L, Corrie P, Eatock M, Valle J, Smith D, Wadsley J, Cunningham D, Pandha H, Neoptolemos JP, Middleton G (2014) The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer. Cancer Immunol Immunother 63(2):175–183. doi:10.1007/s00262-013-1502-y
124. Monk P, Lam E, Mortazavi A, Kendra K, Lesinski GB, Mace TA, Geyer S, Carson WE 3rd, Tahiri S, Bhinder A, Clinton SK, Olencki T (2014) A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma. J Immunother 37(3):180–186. doi:10.1097/CJI.0000000000000023
125. + cells by metastatic tumor cells that express human endogenous retrovirus H. Cancer Res 74(5):1361–1370. doi:10.1158/0008-5472.CAN-13-1349