PD-1 blockade enhances the anti-tumor efficacy of GM-CSF surface-modified bladder cancer stem cells vaccine

Abstract

Eliminating cancer stem cells (CSCs) is a key issue in eradicating tumor. The streptavidin-granulocyte -macrophage colony stimulating factor (SA-GM-CSF) surface-modified bladder cancer stem cells vaccine previously developed using our protein-anchor technology could effectively induce specific immune response for eliminating CSCs. However, program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling in tumor microenvironment results in tumor adaptive immune resistance. Although the CSCs vaccine could increase the number of CD8⁺T-cells, a part of these CD8⁺T-cells expressed PD-1. Moreover, the CSCs vaccine up-regulated the PD-L1 expression of tumor cells, resulting in immune resistance. Adding PD-1 blockade to the CSCs vaccine therapy increased the population of CD4⁺, CD8⁺ and CD8⁺IFN-γ⁺ but not CD4⁺ Foxp3⁺T-cells and induced the highest production of IFN-γ. PD-1 blockade could effectively enhance the functions of tumor-specific T lymphocytes generated by the CSCs vaccine. This combination therapy improved the cure rate among mice, and effectively protected the mice against a second CSCs cell challenge, but not a RM-1 cell challenge. These results indicate that PD-1 blockade combined with the GM-CSF-modified CSCs vaccine effectively induced a strong and specific anti-tumor immune response against bladder cancer. This article is protected by copyright. All rights reserved.

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