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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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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.

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Abbreviations

5-FU:

5-Fluorouracil

Ad5-TRAIL:

Recombinant adenovirus encoding TRAIL

Ag:

Antigen

Batf3:

Basic leucine zipper transcription factor, ATF-like 3

BV650:

Brilliant violet 650

CpG:

CpG-containing oligodeoxynucleotide

DIO:

Diet-induced obesity

HBSS:

Hank’s balanced salt solution

HFF:

High-fat feed

IFN:

Interferon

IL:

Interleukin

i.p.:

Intraperitoneal

IR:

Intrarenal

i.v.:

Intravascular

mAb:

Monoclonal antibody

MACS:

Magnet-associated cell sorting

MDSC:

Myeloid-derived suppressor cell

MHC:

Major histocompatibility complex

PBS:

Phosphate-buffered saline

pDC:

Plasmacytoid dendritic cell

PE:

Phycoerytherin

pfu:

Plaque-forming units

RCC:

Renal cell carcinoma

spDC:

Splenic dendritic cells

TCR:

T-cell receptor

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TRAIL:

TNF-related apoptosis-inducing ligand

WT:

Wild type

References

  1. 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

    Article  PubMed  PubMed Central  Google Scholar 

  2. 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

    Article  PubMed  CAS  Google Scholar 

  3. 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

    Article  Google Scholar 

  4. 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

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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

    Article  CAS  Google Scholar 

  6. 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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. 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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. 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

    Article  PubMed  CAS  Google Scholar 

  9. 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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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 224:98–105

    Article  PubMed  CAS  Google Scholar 

  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 195:517–528

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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 63:685–697

    Article  PubMed  CAS  Google Scholar 

  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 13:265–276

    Article  PubMed  CAS  Google Scholar 

  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 181:346–353

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  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 181:5791–5802

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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 36:1145–1154

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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 3:21–33

    PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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 57:39–50

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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 177:5997–6006

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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 298:297–302

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank the University of Iowa Gene Transfer Vector Core for the production of the Ad5-TRAIL vector. This work was supported by a University of Minnesota Doctoral Dissertation Fellowship (BR James), T90DE022732 from the National Institute of Dental & Craniofacial Research (KG Anderson), a Kidney Cancer Association Research Scholarship administered by the American Urological Association (EL Brincks), and the National Institutes of Health Grants AI084913 (D Masopust) and CA109446 (TS Griffith).

Conflict of interest

B. James, K. Anderson, E. Brincks, T. Kucaba, L. Norian, D. Masopust, and T. Griffith declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Urology, University of Minnesota, 3-125 CCRB, 2231 6th St. SE, Minneapolis, MN, 55455, USA

    Britnie R. James, Erik L. Brincks, Tamara A. Kucaba & Thomas S. Griffith

  2. Department of Microbiology, University of Minnesota, Minneapolis, MN, 55455, USA

    Kristin G. Anderson & David Masopust

  3. Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN, 55455, USA

    Britnie R. James, Kristin G. Anderson, David Masopust & Thomas S. Griffith

  4. Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA

    David Masopust & Thomas S. Griffith

  5. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA

    Thomas S. Griffith

  6. Department of Urology, The University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA

    Lyse A. Norian

  7. Interdisciplinary Graduate Program in Immunology, The University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA

    Lyse A. Norian

  8. Holden Comprehensive Cancer Center, The University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA

    Lyse A. Norian

  9. Center for Immunology, The University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA

    Lyse A. Norian

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  1. Britnie R. James
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  2. Kristin G. Anderson
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  3. Erik L. Brincks
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  4. Tamara A. Kucaba
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  5. Lyse A. Norian
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  6. David Masopust
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  7. Thomas S. Griffith
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Correspondence to Thomas S. Griffith.

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James, B.R., Anderson, K.G., Brincks, E.L. et al. CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma. Cancer Immunol Immunother 63, 1213–1227 (2014). https://doi.org/10.1007/s00262-014-1598-8

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