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01.11.2014 | Original Article

CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma

verfasst von: Britnie R. James, Kristin G. Anderson, Erik L. Brincks, Tamara A. Kucaba, Lyse A. Norian, David Masopust, Thomas S. Griffith

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2014

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Abstract

Tumor progression occurs through the modulation of a number of physiological parameters, including the development of immunosuppressive mechanisms to prevent immune detection and response. Among these immune evasion mechanisms, the mobilization of myeloid-derived suppressor cells (MDSC) is a major contributor to the suppression of antitumor T-cell immunity. Patients with renal cell carcinoma (RCC) show increased MDSC, and methods are being explored clinically to reduce the prevalence of MDSC and/or inhibit their function. In the present study, we investigated the relationship between MDSC and the therapeutic potential of a TRAIL-encoding recombinant adenovirus (Ad5-TRAIL) in combination with CpG-containing oligodeoxynucleotides (Ad5-TRAIL/CpG) in an orthotopic mouse model of RCC. This immunotherapy effectively clears renal (Renca) tumors and enhances survival, despite the presence of a high frequency of MDSC in the spleens and primary tumor-bearing kidneys at the time of treatment. Subsequent analyses revealed that the CpG component of the immunotherapy was responsible for decreasing the frequency of MDSC in Renca-bearing mice; further, treatment with CpG modulated the phenotype and function of MDSC that remained after immunotherapy and correlated with an increased T-cell response. Interestingly, the CpG-dependent alterations in MDSC frequency and function did not occur in tumor-bearing mice complicated with diet-induced obesity. Collectively, these data suggest that in addition to its adjuvant properties, CpG also enhances antitumor responses by altering the number and function of MDSC.

Kusmartsev S, Gabrilovich DI (2006) Role of immature myeloid cells in mechanisms of immune evasion in cancer. Cancer Immunol Immunother 55:237–245. doi:10.1007/s00262-005-0048-z PubMedCrossRefPubMedCentral

Drake CG, Jaffee E, Pardoll DM (2006) Mechanisms of immune evasion by tumors. Adv Immunol 90:51–81. doi:10.1016/S0065-2776(06)90002-9 PubMedCrossRef

Mittal D, Gubin MM, Schreiber RD, Smyth MJ (2014) New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr Opin Immunol 27C:16–25. doi:10.1016/j.coi.2014.01.004 CrossRef

Ostrand-Rosenberg S (2010) Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother 59:1593–1600. doi:10.1007/s00262-010-0855-8 PubMedCrossRefPubMedCentral

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. Sem Cancer Biol 22:275–281. doi:10.1016/j.semcancer.2012.01.011 CrossRef

Ko JS, Rayman P, Ireland J, Swaidani S, Li G, Bunting KD, Rini B, Finke JH, Cohen PA (2010) Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res 70:3526–3536. doi:10.1158/0008-5472.CAN-09-3278 PubMedCrossRefPubMedCentral

Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69:1553–1560. doi:10.1158/0008-5472.CAN-08-1921 PubMedCrossRefPubMedCentral

Ochoa AC, Zea AH, Hernandez C, Rodriguez PC (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13:721s–726s. doi:10.1158/1078-0432.CCR-06-2197 PubMedCrossRef

Fridlender ZG, Sun J, Singhal S, Kapoor V, Cheng G, Suzuki E, Albelda SM (2010) Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms. Mol Ther 18:1947–1959. doi:10.1038/mt.2010.159 PubMedCrossRefPubMedCentral

10.

Kao J, Ko EC, Eisenstein S, Sikora AG, Fu S, Chen SH (2011) Targeting immune suppressing myeloid-derived suppressor cells in oncology. Crit Rev Oncol Hematol 77:12–19. doi:10.1016/j.critrevonc.2010.02.004 PubMedCrossRefPubMedCentral

11.

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 (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15:2148–2157. doi:10.1158/1078-0432.CCR-08-1332 PubMedCrossRef

12.

Najjar YG, Finke JH (2013) Clinical perspectives on targeting of myeloid derived suppressor cells in the treatment of cancer. Front Oncol 3:49. doi:10.3389/fonc.2013.00049 PubMedCrossRefPubMedCentral

13.

Xia S, Sha H, Yang L, Ji Y, Ostrand-Rosenberg S, Qi L (2011) Gr-1+ CD11b+ myeloid-derived suppressor cells suppress inflammation and promote insulin sensitivity in obesity. J Biol Chem 286:23591–23599. doi:10.1074/jbc.M111.237123 PubMedCrossRefPubMedCentral

14.

Matsuzaki J, Tsuji T, Chamoto K, Takeshima T, Sendo F, Nishimura T (2003) Successful elimination of memory-type CD8+ T cell subsets by the administration of anti-Gr-1 monoclonal antibody in vivo. Cell Immunol 224:98–105PubMedCrossRef

15.

Dalod M, Salazar-Mather TP, Malmgaard L, Lewis C, Asselin-Paturel C, Briere F, Trinchieri G, Biron CA (2002) Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. J Exp Med 195:517–528PubMedCrossRefPubMedCentral

16.

Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, Martin F, Apetoh L, Rebe C, Ghiringhelli F (2010) 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 70:3052–3061. doi:10.1158/0008-5472.CAN-09-3690 PubMedCrossRef

17.

Mozaffari F, Lindemalm C, Choudhury A, Granstam-Bjorneklett H, Lekander M, Nilsson B, Ojutkangas ML, Osterborg A, Bergkvist L, Mellstedt H (2009) Systemic immune effects of adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide and/or radiotherapy in breast cancer: a longitudinal study. Cancer Immunol Immunother 58:111–120. doi:10.1007/s00262-008-0530-5 PubMedCrossRef

18.

Mozaffari F, Lindemalm C, Choudhury A, Granstam-Bjorneklett H, Helander I, Lekander M, Mikaelsson E, Nilsson B, Ojutkangas ML, Osterborg A, Bergkvist L, Mellstedt H (2007) NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radio-therapy. Br J Cancer 97:105–111. doi:10.1038/sj.bjc.6603840 PubMedCrossRefPubMedCentral

19.

Kemp TJ, Kim J-S, Crist SA, Griffith TS (2003) Induction of necrotic tumor cell death by TRAIL/Apo-2L. Apoptosis 8:587–599PubMedCrossRef

20.

Norian LA, Kresowik TP, Rosevear HM, James BR, Rosean TR, Lightfoot AJ, Kucaba TA, Schwarz C, Weydert CJ, Henry MD, Griffith TS (2012) Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF-related apoptosis-inducing ligand (TRAIL)/CpG immunotherapy. PLoS One 7:e31085. doi:10.1371/journal.pone.0031085 PubMedCrossRefPubMedCentral

21.

Anderson KG, Mayer-Barber K, Sung H, Beura L, James BR, Taylor JJ, Qunaj L, Griffith TS, Vezys V, Barber DL, Masopust D (2014) Intravascular staining for discrimination of vascular and tissue leukocytes. Nat Protoc 9:209–222. doi:10.1038/nprot.2014.005 PubMedCrossRef

22.

James BR, Tomanek-Chalkley A, Askeland EJ, Kucaba T, Griffith TS, Norian LA (2012) Diet-induced obesity alters dendritic cell function in the presence and absence of tumor growth. J Immunol 189:1311–1321. doi:10.4049/jimmunol.1100587 PubMedCrossRefPubMedCentral

23.

Hrushesky WJ, Murphy GP (1973) Investigation of a new renal tumor model. J Surg Res 15:327–336PubMedCrossRef

24.

VanOosten RL, Griffith TS (2007) Activation of tumor-specific CD8⁺ T Cells after intratumoral Ad5-TRAIL/CpG oligodeoxynucleotide combination therapy. Cancer Res 67:11980–11990PubMedCrossRef

25.

James BR, Brincks EL, Kucaba TA, Boon L, Griffith TS (2014) Effective TRAIL-based immunotherapy requires both plasmacytoid and CD8a DC. Cancer Immunol Immunother 63:685–697PubMedCrossRef

26.

Hanson HL, Donermeyer DL, Ikeda H, White JM, Shankaran V, Old LJ, Shiku H, Schreiber RD, Allen PM (2000) Eradication of established tumors by CD8+ T cell adoptive immunotherapy. Immunity 13:265–276PubMedCrossRef

27.

Kusmartsev S, Eruslanov E, Kubler H, Tseng T, Sakai Y, Su Z, Kaliberov S, Heiser A, Rosser C, Dahm P, Siemann D, Vieweg J (2008) Oxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma. J Immunol 181:346–353PubMedCrossRef

28.

Rocha FG, Chaves KC, Chammas R, Peron JP, Rizzo LV, Schor N, Bellini MH (2010) Endostatin gene therapy enhances the efficacy of IL-2 in suppressing metastatic renal cell carcinoma in mice. Cancer Immunol Immunother 59:1357–1365. doi:10.1007/s00262-010-0865-6 PubMedCrossRef

29.

Salup RR, Back TC, Wiltrout RH (1987) Successful treatment of advanced murine renal cell cancer by bicompartmental adoptive chemoimmunotherapy. J Immunol 138:641–647PubMed

30.

Gabrilovich DI, Bronte V, Chen SH, Colombo MP, Ochoa A, Ostrand-Rosenberg S, Schreiber H (2007) The terminology issue for myeloid-derived suppressor cells. Cancer Res 67:425; author reply 426. doi:10.1158/0008-5472.CAN-06-3037

31.

Youn JI, Nagaraj S, Collazo M, Gabrilovich DI (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181:5791–5802PubMedCrossRefPubMedCentral

32.

Movahedi K, Guilliams M, Van den Bossche J, Van den Bergh R, Gysemans C, Beschin A, De Baetselier P, Van Ginderachter JA (2008) Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111:4233–4244. doi:10.1182/blood-2007-07-099226 PubMedCrossRef

33.

Kusmartsev S, Gabrilovich DI (2005) STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J Immunol 174:4880–4891PubMedCrossRef

34.

Greifenberg V, Ribechini E, Rossner S, Lutz MB (2009) Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development. Eur J Immunol 39:2865–2876. doi:10.1002/eji.200939486 PubMedCrossRef

35.

Ueha S, Shand FH, Matsushima K (2011) Myeloid cell population dynamics in healthy and tumor-bearing mice. Int Immunopharmacol 11:783–788. doi:10.1016/j.intimp.2011.03.003 PubMedCrossRef

36.

Messai Y, Noman MZ, Derouiche A, Kourda N, Akalay I, Hasmim M, Stasik I, Ben Jilani S, Chebil M, Caignard A, Azzarone B, Gati A, Ben Ammar Elgaaied A, Chouaib S (2010) Cytokeratin 18 expression pattern correlates with renal cell carcinoma progression: relationship with Snail. Int J Oncol 36:1145–1154PubMed

37.

Shirota Y, Shirota H, Klinman DM (2012) Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells. J Immunol 188:1592–1599. doi:10.4049/jimmunol.1101304 PubMedCrossRefPubMedCentral

38.

Bunt SK, Yang L, Sinha P, Clements VK, Leips J, Ostrand-Rosenberg S (2007) Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 67:10019–10026. doi:10.1158/0008-5472.CAN-07-2354 PubMedCrossRef

39.

Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nature Rev Immunol 11:85–97. doi:10.1038/nri2921 CrossRef

40.

Okwan-Duodu D, Umpierrez GE, Brawley OW, Diaz R (2013) Obesity-driven inflammation and cancer risk: role of myeloid derived suppressor cells and alternately activated macrophages. Am J Cancer Res 3:21–33PubMedPubMedCentral

41.

Litterman AJ, Zellmer DM, Grinnen KL, Hunt MA, Dudek AZ, Salazar AM, Ohlfest JR (2013) Profound impairment of adaptive immune responses by alkylating chemotherapy. J Immunol 190:6259–6268. doi:10.4049/jimmunol.1203539 PubMedCrossRefPubMedCentral

42.

Krieg AM (2012) CpG still rocks! Update on an accidental drug. Nucleic Acid Ther 22:77–89. doi:10.1089/nat.2012.0340 PubMed

43.

Zoglmeier C, Bauer H, Norenberg D, Wedekind G, Bittner P, Sandholzer N, Rapp M, Anz D, Endres S, Bourquin C (2011) CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice. Clin Cancer Res 17:1765–1775. doi:10.1158/1078-0432.CCR-10-2672 PubMedCrossRef

44.

Suzuki K, Suda T, Naito T, Ide K, Chida K, Nakamura H (2005) Impaired toll-like receptor 9 expression in alveolar macrophages with no sensitivity to CpG DNA. Am J Respir Crit Care Med 171:707–713. doi:10.1164/rccm.200408-1078OC PubMedCrossRef

45.

Laber DA (2006) Risk factors, classification, and staging of renal cell cancer. Med Oncol 23:443–454. doi:10.1385/MO:23:4:443 PubMedCrossRef

46.

Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830. doi:10.1172/JCI19451 PubMedCrossRefPubMedCentral

47.

Lee IS, Shin G, Choue R (2010) Shifts in diet from high fat to high carbohydrate improved levels of adipokines and pro-inflammatory cytokines in mice fed a high-fat diet. Endocrine J 57:39–50CrossRef

48.

Fenton JI, Nunez NP, Yakar S, Perkins SN, Hord NG, Hursting SD (2009) Diet-induced adiposity alters the serum profile of inflammation in C57BL/6N mice as measured by antibody array. Diabetes Obes Metab 11:343–354. doi:10.1111/j.1463-1326.2008.00974.x PubMedCrossRef

49.

Karlsson EA, Sheridan PA, Beck MA (2010) Diet-induced obesity in mice reduces the maintenance of influenza-specific CD8+ memory T cells. J Nutr 140:1691–1697. doi:10.3945/jn.110.123653 PubMedCrossRefPubMedCentral

50.

Karlsson EA, Sheridan PA, Beck MA (2010) Diet-induced obesity impairs the T cell memory response to influenza virus infection. J Immunol 184:3127–3133. doi:10.4049/jimmunol.0903220 PubMedCrossRef

51.

Kim CS, Lee SC, Kim YM, Kim BS, Choi HS, Kawada T, Kwon BS, Yu R (2008) Visceral fat accumulation induced by a high-fat diet causes the atrophy of mesenteric lymph nodes in obese mice. Obesity (Silver Spring) 16:1261–1269. doi:10.1038/oby.2008.55 CrossRef

52.

Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239–3246. doi:10.2337/db08-0872 PubMedCrossRefPubMedCentral

53.

Smith AG, Sheridan PA, Tseng RJ, Sheridan JF, Beck MA (2009) Selective impairment in dendritic cell function and altered antigen-specific CD8+ T-cell responses in diet-induced obese mice infected with influenza virus. Immunology 126:268–279. doi:10.1111/j.1365-2567.2008.02895.x PubMedCrossRefPubMedCentral

54.

Verwaerde C, Delanoye A, Macia L, Tailleux A, Wolowczuk I (2006) Influence of high-fat feeding on both naive and antigen-experienced T-cell immune response in DO10.11 mice. Scand J Immunol 64:457–466. doi:10.1111/j.1365-3083.2006.01791.x PubMedCrossRef

55.

Mito N, Kaburagi T, Yoshino H, Imai A, Sato K (2006) Oral-tolerance induction in diet-induced obese mice. Life Sci 79:1056–1061. doi:10.1016/j.lfs.2006.03.015 PubMedCrossRef

56.

Cui J, Xiao Y, Shi YH, Wang B, Le GW (2012) Lipoic acid attenuates high-fat-diet-induced oxidative stress and B-cell-related immune depression. Nutrition 28:275–280. doi:10.1016/j.nut.2011.10.016 PubMedCrossRef

57.

Miyazaki Y, Iwabuchi K, Iwata D, Miyazaki A, Kon Y, Niino M, Kikuchi S, Yanagawa Y, Kaer LV, Sasaki H, Onoe K (2008) Effect of high fat diet on NKT cell function and NKT cell-mediated regulation of Th1 responses. Scand J Immunol 67:230–237. doi:10.1111/j.1365-3083.2007.02062.x PubMedCrossRef

58.

Macia L, Delacre M, Abboud G, Ouk TS, Delanoye A, Verwaerde C, Saule P, Wolowczuk I (2006) Impairment of dendritic cell functionality and steady-state number in obese mice. J Immunol 177:5997–6006PubMedCrossRef

59.

Batra A, Okur B, Glauben R, Erben U, Ihbe J, Stroh T, Fedke I, Chang HD, Zeitz M, Siegmund B (2010) Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology 151:56–62. doi:10.1210/en.2009-0565 PubMedCrossRef

60.

Tian Z, Sun R, Wei H, Gao B (2002) Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem Biophys Res Commun 298:297–302PubMedCrossRef

Titel: CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma
verfasst von: Britnie R. James
Kristin G. Anderson
Erik L. Brincks
Tamara A. Kucaba
Lyse A. Norian
David Masopust
Thomas S. Griffith
Publikationsdatum: 01.11.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 11/2014
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-014-1598-8

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CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma

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