Combination immunotherapy with IL-2 surface-modified tumor cell vaccine and PD-1 blockade against renal cell carcinoma.

Immunotherapy may be an effective way to prevent postoperative recurrence of renal cell carcinoma. Streptavidin-interleukin-2 (SA-IL-2) surface-modified tumor cell vaccine developed through our protein-anchor technology could induce specific anti-tumor T-cell response, but this immunotherapy can not completely eradicate the tumor. These effector T-cells highly expressed program death receptor-1 (PD-1), and the expression of program death ligand-1 (PD-L1) in tumor environment also was up-regulated after the SA-IL-2-modified vaccine therapy. PD-1/PD-L1 interaction promotes tumor immune evasion. Adding PD-1 blockade to SA-IL-2-modified vaccine therapy increased the number of CD4+ , CD8+ and CD8+ IFN-γ+ but not CD4+ Foxp3+ T-cells. PD-1 blockade could rescue the activity of tumor-specific T lymphocytes induced by the SA-IL-2-modified vaccine. The combination therapy delayed tumor growth and protected mice against a second Renca cells but not melanoma cells challenge. Taken together, PD-1 blockade could reverse the immune evasion in the treatment with SA-IL-2-modified vaccine, and eventually induce a stronger specific anti-tumor immune response against renal cell carcinoma. This article is protected by copyright. All rights reserved.