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

PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer.
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Shi X, Zhang X, Li J, Zhao H, Mo L, Shi X, Hu Z, Gao J, Tan W,


Shi X, Zhang X, Li J, Zhao H, Mo L, Shi X, Hu Z, Gao J, Tan W, (click to view)

Shi X, Zhang X, Li J, Zhao H, Mo L, Shi X, Hu Z, Gao J, Tan W,

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Cancer letters 2017 08 08406() 27-35 pii 10.1016/j.canlet.2017.07.029

Abstract

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.

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