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

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

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1213-1227
Number of pages15
JournalCancer Immunology, Immunotherapy
Volume63
Issue number11
DOIs
StatePublished - Nov 2014

Bibliographical note

Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.

Keywords

  • Diet-induced obesity
  • Immunotherapy
  • MDSC
  • RCC
  • TRAIL

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