PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer

类型： 血细胞

作者：Shi X, Zhang X, Li J, Zhao H, Mo L, Shi X, Hu Z, Gao J, Tan W
期刊：Cancer Lett. 2017 Oct 10;406:27-35.
阅读原文

Program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling plays an important role in tumor adaptive immune resistance. The streptavidin-granulocyte-macrophage colony stimulating factor (SA-GM-CSF) surface-modified tumor cells vaccine developed through our novel protein-anchor technology could significantly promote the activation of dendritic cells. Although GM-CSF vaccine could significantly increase the number of tumor-specific CD8⁺T-cells, the majority of these CD8⁺T-cells expressed PD-1. Moreover, GM-CSF vaccine up-regulated the PD-L1 expression of tumor cells, resulting in immune resistance. Adding PD-1/PD-L1 blockade to GM-CSF vaccine therapy could significantly increase the population of CD4⁺ T, CD8⁺ T and CD8⁺ IFN-γ⁺ T but not CD4⁺ Foxp3⁺ T-cells and induced the highest production of IFN-γ. PD-1/PD-L1 blockade could effectively rescue the tumor-specific T lymphocytes generated by the GM-CSF vaccine, resulting in consistent tumor rejection. Taken together, PD-1/PD-L1 blockade combined with SA-GM-CSF-modified vaccine could effectively induce a strong specific antitumor immune response against prostate cancer.