Myeloid derived suppressor cells – a new therapeutic target in the treatment of cancer

Journal for ImmunoTherapy of Cancer

William E Carson³  Joseph Markowitz²  Robert Wesolowski¹ 

[1] Division of Medical Oncology, B401 Starling Loving Hall, W10th Avenue, Columbus, OH 43210, USA;Division of Medical Oncology, 406C Starling Loving Hall 320 W 10th Ave, Columbus, OH 43210, USA;The Ohio State University Comprehensie Cancer Center, N911 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210, USA

关键词: Cancer vaccines;    Tumor immunology;    Immunotherapy;    Myeloid derived suppressor cells;   

Others  :  815027
DOI  :  10.1186/2051-1426-1-10

 received in 2013-01-28, accepted in 2013-06-14,  发布年份 2013

【 摘 要 】

Myeloid Derived Suppressor Cells (MDSC) are a heterogeneous population of immature myeloid cells that are increased in states of cancer, inflammation and infection. In malignant states, MDSC are induced by tumor secreted growth factors. MDSC play an important part in suppression of host immune responses through several mechanisms such as production of arginase 1, release of reactive oxygen species and nitric oxide and secretion of immune-suppressive cytokines. This leads to a permissive immune environment necessary for the growth of malignant cells. MDSC may also contribute to angiogenesis and tumor invasion. This review focuses on currently available strategies to inhibit MDSC in the treatment of cancer.

【 授权许可】

   
2013 Wesolowski et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Gabrilovich DI, Nagaraj S: Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009, 9:162-174.
• [2]Greten TF, Manns MP, Korangy F: Myeloid derived suppressor cells in human diseases. Int Immunopharmacol 2011, 11:802-807.
• [3]Filipazzi P, Huber V, Rivoltini L: Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother 2012, 61:255-263.
• [4]Mundy-Bosse BL, Young GS, Bauer T, Binkley E, Bloomston M, Bill MA, Bekaii-Saab T, Carson WE 3rd, Lesinski GB: Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4+ T cells from patients with GI malignancy. Cancer Immunol Immunother 2011, 60:1269-1279.
• [5]Movahedi K, Guilliams M, Van den Bossche J, Van den Bergh R, Gysemans C, Beschin A, De Baetselier P, Van Ginderachter JA: Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 2008, 111:4233-4244.
• [6]Sawanobori Y, Ueha S, Kurachi M, Shimaoka T, Talmadge JE, Abe J, Shono Y, Kitabatake M, Kakimi K, Mukaida N, Matsushima K: Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood 2008, 111:5457-5466.
• [7]Gabrilovich DI, Ostrand-Rosenberg S, Bronte V: Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012, 12:253-268.
• [8]Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI: Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 2001, 166:678-689.
• [9]Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman PA, Wood L, Garcia J, Dreicer R, Bukowski R, Finke JH: Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 2009, 15:2148-2157.
• [10]Gabitass RF, Annels NE, Stocken DD, Pandha HA, Middleton GW: Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother 2011, 60:1419-1430.
• [11]Montero AJ, Diaz-Montero CM, Kyriakopoulos CE, Bronte V, Mandruzzato S: Myeloid-derived suppressor cells in cancer patients: a clinical perspective. J Immunother 2012, 35:107-115.
• [12]Malmberg KJ: Effective immunotherapy against cancer: a question of overcoming immune suppression and immune escape. Cancer Immunol Immunother 2004, 53:879-892.
• [13]Mundy-Bosse BL, Lesinski GB, Jaime-Ramirez AC, Benninger K, Khan M, Kuppusamy P, Guenterberg K, Kondadasula SV, Chaudhury AR, La Perle KM, Kreiner M, Young G, Guttridge DC, Carson WE 3rd: Myeloid-derived suppressor cell inhibition of the IFN response in tumor-bearing mice. Cancer Res 2011, 71:5101-5110.
• [14]Kusmartsev S, Cheng F, Yu B, Nefedova Y, Sotomayor E, Lush R, Gabrilovich D: All-trans–retinoic acid eliminates immature myeloid cells from tumor bearing mice and improves the effect of vaccination. Cancer Res 2003, 63:4441-4449.
• [15]Ishizaki H, Manuel ER, Song GY, Srivastava T, Sun S, Diamond DJ, Ellenhorn : Modified vaccinia Ankara expressing survivin combined with gemcitabine generates specific antitumor effects in a murine pancreatic carcinoma model. Cancer Immunol Immunother 2011, 60:99-109.
• [16]Weiss T, Vitacolonna M, Zöller M: The efficacy of an IL-1alpha vaccine depends on IL-1RI availability and concomitant myeloid-derived suppressor cell reduction. J Immunother 2009, 32:552-564.
• [17]De Santo C, Serafini P, Marigo I, Dolcetti L, Bolla M, Del Soldato P, Melani C, Guiducci C, Colombo MP, Iezzi M, Musiani P, Zanovello P, Bronte V: Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci USA 2005, 102:4185-4190.
• [18]Nagaraj S, Youn JI, Weber H, Iclozan C, Lu L, Cotter MJ, Meyer C, Becerra CR, Fishman M, Antonia S, Sporn MB, Liby KT, Rawal B, Lee JH, Gabrilovich DI: Anti-inflammatory triterpenoid blocks immune suppressive function of MDSCs and improves immune response in cancer. Clin Cancer Res 2010, 16:1812-1823.
• [19]Nakashima H, Terabe M, Berzofsky JA, Husain SR, Puri RK: A novel combination immunotherapy for cancer by IL-13Rα2-targeted DNA vaccine and immunotoxin in murine tumor models. J Immunol 2011, 187:4935-4946.
• [20]Bose A, Taylor JL, Alber S, Watkins SC, Garcia JA, Rini BI, Ko JS, Cohen PA, Finke JH, Storkus WJ: Sunitinib facilitates the activation and recruitment of therapeutic anti-tumor immunity in concert with specific vaccination. Int J Cancer 2011, 129:2158-2170.
• [21]Ko HJ, Kim YJ, Kim YS, Chang WS, Ko SY, Chang SY, Sakaguchi S, Kang CY: A combination of chemoimmunotherapies can efficiently break self-tolerance and induce antitumor immunity in a tolerogenic murine tumor model. Cancer Res 2007, 67:7477-7486.
• [22]Tseng CW, Hung CF, Alvarez RD, Trimble C, Huh WK, Kim D, Chuang CM, Lin CT, Tsai YC, He L, Monie A, Wu TC: Pretreatment with cisplatin enhances E7-specific CD8+ T-Cell-mediated antitumor immunity induced by DNA vaccination. Clin Cancer Res 2008, 14:3185-3192.
• [23]Melani C, Sangaletti S, Barazzetta FM, Werb Z, Colombo MP: Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma. Cancer Res 2007, 67:11438-11446.
• [24]Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W, Dolcetti L, Bronte V, Borrello I: Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 2006, 203:2691-2702.
• [25]Rodriguez PC, Zea AH, Culotta KS, Zabaleta J, Ochoa JB, Ochoa AC: Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem 2002, 277:21123-21129.
• [26]Schreiber RD, Old LJ, Smyth MJ: Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 2011, 331:1565-1570.
• [27]Sinha P, Parker KH, Horn L, Ostrand-Rosenberg S: Tumor-induced myeloid-derived suppressor cell function is independent of IFNγ and IL-4Rα. Eur J Immunol 2012, 42:2052-2059.
• [28]Nagaraj S, Schrum AG, Cho HI, Celis E, Gabrilovich DI: Mechanism of T cell tolerance induced by myeloid-derived suppressor cells. J Immunol 2010, 184:3106-3116.
• [29]Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D, De Palma A, Mauri P, Monegal A, Rescigno M, Savino B, Colombo P, Jonjic N, Pecanic S, Lazzarato L, Fruttero R, Gasco A, Bronte V, Viola A: Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med 2011, 208:1949-1962.
• [30]Fiorucci S, Santucci L, Cirino G, Mencarelli A, Familiari L, Soldato PD, Morelli A: IL-1 beta converting enzyme is a target for nitric oxide-releasing aspirin: new insights in the antiinflammatory mechanism of nitric oxide-releasing nonsteroidal antiinflammatory drugs. J Immunol 2000, 165:5245-5254.
• [31]Thimmulappa RK, Fuchs RJ, Malhotra D, Scollick C, Traore K, Bream JH, Trush MA, Liby KT, Sporn MB, Kensler TW, Biswal S: Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils. Antioxid Redox Signal 2007, 9:1963-1970.
• [32]Ahmad R, Raina D, Meyer C, Kufe D: Triterpenoid CDDO-methyl ester inhibits the Janus-activated kinase-1 (JAK1)- > signal transducer and activator of transcription-3 (STAT3) pathway by direct inhibition of JAK1 and STAT3. Cancer Res 2008, 68:2920-2926.
• [33]Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S: Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 2007, 67:4507-4513.
• [34]Rodriguez PC, Hernandez CP, Quiceno D, Dubinett SM, Zabaleta J, Ochoa JB, Gilbert J, Ochoa AC: Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med 2005, 202:931-939.
• [35]Talmadge JE, Hood KC, Zobel LC, Shafer LR, Coles M, Toth B: Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion. Int Immunopharmacol 2007, 7:140-151.
• [36]Veltman JD, Lambers ME, van Nimwegen M, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP: COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer 2010, 10:464. BioMed Central Full Text
• [37]Stuehr DJ, Kwon NS, Nathan CF, Griffith OW, Feldman PL, Wiseman J: N omega-hydroxy-l-arginine is an intermediate in the biosynthesis of nitric oxide from l-arginine. J Biol Chem 1991, 266:6259-6263.
• [38]Serafini P, Mgebroff S, Noonan K, Borrello I: Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res 2008, 68:5439-5449.
• [39]Reisser D, Onier-Cherix N, Jeannin JF: Arginase activity is inhibited by L-NAME, both in vitro and in vivo. J Enzyme Inhib Med Chem 2002, 17:267-270.
• [40]Nanni S, Benvenuti V, Grasselli A, Priolo C, Aiello A, Mattiussi S, Colussi C, Lirangi V, Illi B, D’Eletto M, Cianciulli AM, Gallucci M, De Carli P, Sentinelli S, Mottolese M, Carlini P, Strigari L, Finn S, Mueller E, Arcangeli G, Gaetano C, Capogrossi MC, Donnorso RP, Bacchetti S, Sacchi A, Pontecorvi A, Loda M, Farsetti A: Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer. J Clin Invest 2009, 119:1093-1108.
• [41]Capuano G, Rigamonti N, Grioni M, Freschi M, Bellone M: Modulators of arginine metabolism support cancer immunosurveillance. BMC Immunol 2009, 10:1. BioMed Central Full Text
• [42]Rigamonti N, Capuano G, Ricupito A, Jachetti E, Grioni M, Generoso L, Freschi M, Bellone M: Modulators of arginine metabolism do not impact on peripheral T-cell tolerance and disease progression in a model of spontaneous prostate cancer. Clin Cancer Res 2011, 17:1012-1023.
• [43]Cheng P, Corzo CA, Luetteke N, Yu B, Nagaraj S, Bui MM, Ortiz M, Nacken W, Sorg C, Vogl T, Roth J, Gabrilovich DI: Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J Exp Med 2008, 205:2235-2249.
• [44]Turovskaya O, Foell D, Sinha P, Vogl T, Newlin R, Nayak J, Nguyen M, Olsson A, Nawroth PP, Bierhaus A, Varki N, Kronenberg M, Freeze HH, Srikrishna G: RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Carcinogenesis 2008, 29:2035-2043.
• [45]Sinha P, Okoro C, Foell D, Freeze HH, Ostrand-Rosenberg S, Srikrishna G: Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol 2008, 181:4666-4675.
• [46]Priceman SJ, Sung JL, Shaposhnik Z, Burton JB, Torres-Collado AX, Moughon DL, Johnson M, Lusis AJ, Cohen DA, Iruela-Arispe ML, Wu L: Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy. Blood 2010, 115:1461-1471.
• [47]Xu J, Escamilla J, Mok S, David J, Priceman S, West B, Bollag G, McBride W, Wu L: CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer. Cancer Res 2013, 73:2782-2794.
• [48]Mor S, Nagler A, Barak V, Handzel ZT, Geller-Bernstein C, Fabian I: Histamine enhances granulocyte-macrophage colony-stimulating factor and interleukin-6 production by human peripheral blood mononuclear cells. J Leukoc Biol 1995, 58:445-450.
• [49]Yang XD, Ai W, Asfaha S, Bhagat G, Friedman RA, Jin G, Park H, Shykind B, Diacovo TG, Falus A, Wang TC: Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b + Ly6G + immature myeloid cells. Nat Med 2011, 17:87-95.
• [50]Thoren FB, Aurelius J, Martner A: Antitumor properties of histamine in vivo. Nat Med 2011, 17:537.
• [51]Zheng Y, Xu M, Li X, Jia J, Fan K, Lai G: Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells. Mol Immunol 2012, 54:74-83.
• [52]He D, Li H, Yusuf N, Elmets CA, Li J, Mountz JD, Xu H: IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. J Immunol 2010, 184:2281-2288.
• [53]Bastien J, Rochette-Egly C: Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene 2004, 328:1-16.
• [54]Hengesbach LM, Hoag KA: Physiological concentrations of retinoic acid favor myeloid dendritic cell development over granulocyte development in cultures of bone marrow cells from mice. J Nutr 2004, 134:2653-2659.
• [55]Kusmartsev S, Su Z, Heiser A, Dannull J, Eruslanov E, Kübler H, Yancey D, Dahm P, Vieweg J: Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma. Clin Cancer Res 2008, 14:8270-8278.
• [56]Mirza N, Fishman M, Fricke I, Dunn M, Neuger AM, Frost TJ, Lush RM, Antonia S, Gabrilovich DI: All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res 2006, 66:9299-9307.
• [57]Wiers KM, Lathers DM, Wright MA, Young MR: Vitamin D3 treatment to diminish the levels of immune suppressive CD34 cells increases the effectiveness of adoptive immunotherapy. J Immunother 2000, 23:115-124.
• [58]Lathers DM, Clark JI, Achille NJ, Young MR: Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol Immunother 2004, 53:422-430.
• [59]Roda JM, Parihar R, Carson WE 3rd: CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells. J Immunol 2005, 175:1619-1627.
• [60]Zoglmeier C, Bauer H, Nörenberg D, Wedekind G, Bittner P, Sandholzer N, Rapp M, Anz D, Endres S, Bourquin C: CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice. Clin Cancer Res 2011, 17:1765-1775.
• [61]Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S: Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 2007, 179:977-983.
• [62]Steding CE, Wu ST, Zhang Y, Jeng MH, Elzey BD, Kao C: The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis. Immunology 2011, 133:221-238.
• [63]Chinnasamy D, Yu Z, Kerkar SP, Zhang L, Morgan RA, Restifo NP, Rosenberg SA: Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin Cancer Res 2012, 18:1672-1683.
• [64]Kerkar SP, Goldszmid RS, Muranski P, Chinnasamy D, Yu Z, Reger RN, Leonardi AJ, Morgan RA, Wang E, Marincola FM, Trinchieri G, Rosenberg SA, Restifo NP: IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. J Clin Invest 2011, 121:4746-4757.
• [65]Rodan GA, Fleisch HA: Bisphosphonates: mechanisms of action. J Clin Invest 1996, 97:2692-2696.
• [66]Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002, 109:625-637.
• [67]Porembka MR, Mitchem JB, Belt BA, Hsieh CS, Lee HM, Herndon J, Gillanders WE, Linehan DC, Goedegebuure P: Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth. Cancer Immunol Immunother 2012, 61:1373-1385.
• [68]Ugel S, Delpozzo F, Desantis G, Papalini F, Simonato F, Sonda N, Zilio S, Bronte V: Therapeutic targeting of myeloid-derived suppressor cells. Curr Opin Pharmacol 2009, 9:470-481.
• [69]Sansone P, Bromberg J: Targeting the Interleukin-6/Jak/Stat pathway in human malignancies. J Clin Oncol 2012, 30:1005-1014.
• [70]Lin L, Deangelis S, Foust E, Fuchs J, Li C, Li PK, Schwartz EB, Lesinski GB, Benson D, Lü J, Hoyt D, Lin J: A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells. Mol Cancer 2010, 9:217. BioMed Central Full Text
• [71]Bill MA, Fuchs JR, Li C, Yui J, Bakan C, Benson DM Jr, Schwartz EB, Abdelhamid D, Lin J, Hoyt DG, Fossey SL, Young GS, Carson WE 3rd, Li PK, Lesinski GB: The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity. Mol Cancer 2010, 9:165. BioMed Central Full Text
• [72]Lu P, Yu B, Xu J: Cucurbitacin B regulates immature myeloid cell differentiation and enhances antitumor immunity in patients with lung cancer. Cancer Biother Radiopharm 2012, 27:495-503.
• [73]Fricke I, Mirza N, Dupont J, Lockhart C, Jackson A, Lee JH, Sosman JA, Gabrilovich DI: Treatment of cancer patients with VEGF-Trap overcomes defects in DC differentiation but is insufficient to improve antigen-specific immune responses. Clin Cancer Res 2007, 13:4840-4848.
• [74]Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC: Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 2009, 69:1553-1560.
• [75]Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM: Gemcitabine selectively eliminates splenic Gr-1+/CD11b + myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 2005, 11:6713-6721.
• [76]Le HK, Graham L, Cha E, Morales JK, Manjili MH, Bear HD: Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol 2009, 9:900-909.
• [77]Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, Martin F, Apetoh L, Rébé C, Ghiringhelli F: 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 2010, 70:3052-3061.
• [78]Naiditch H, Shurin MR, Shurin GV: Targeting myeloid regulatory cells in cancer by chemotherapeutic agents. Immunol Res 2011, 50:276-285.
• [79]Rao A, Taylor JL, Chi-Sabins N, Kawabe M, Gooding WE, Storkus WJ: Combination therapy with HSP90 inhibitor 17-DMAG reconditions the tumor microenvironment to improve recruitment of therapeutic T cells. Cancer Res 2012, 72:3196-3206.
• [80]Ostrand-Rosenberg S, Sinha P, Chornoguz O, Ecker C: Regulating the suppressors: apoptosis and inflammation govern the survival of tumor-induced myeloid-derived suppressor cells (MDSC). Cancer Immunol Immunother 2012, 61:1319-1325.
• [81]Sumida K, Wakita D, Narita Y, Masuko K, Terada S, Watanabe K, Satoh T, Kitamura H, Nishimura T: Anti-IL-6 receptor mAb eliminates myeloid-derived suppressor cells and inhibits tumor growth by enhancing T-cell responses. Eur J Immunol 2012, 42:2060-2072.