Myeloid-derived suppressor cells (MDSC) are immature, activated myeloid cells that can suppress T cell function via multiple mechanisms and dampen antitumor immunity. As with many tumor models, we found a high frequency of MDSC in the primary kidney tumor, spleen, and lung metastases in an orthotopic model of advanced renal cell carcinoma (RCC). MDSC from both primary tumor and spleen suppressed T cell proliferation in vitro. However, following treatment of the primary kidney tumor with a recombinant adenovirus encoding TRAIL (Ad-TRAIL) in combination with CpG ODN, MDSC numbers decreased at all aforementioned locations and a robust systemic CD8 T cell-mediated antitumor immune response was initiated that was ultimately responsible for clearing the primary RCC tumors and lung metastases. Subsequent analysis revealed that CpG ODN alone was able to directly modulate MDSC frequency and phenotype at the primary tumor site and metastatic lung, resulting in a more “mature” phenotype as seen by increases in CD40, CD80, and CD11c and decreases in Gr-1. Interestingly, concomitant depletion of MDSC, which alone lead to tumor regression, did not exhibit any synergistic effects with therapy, suggesting that Ad-TRAIL/CpG alone overcomes MDSC suppression. These data suggest that while CpG ODN may play many roles contributing to the antitumor immune response, one important role appears to be the modulation of the suppressive MDSC population.
- Copyright © 2013 by The American Association of Immunologists, Inc.