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

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 CSCs 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 upregulated 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 antitumor immune response against bladder cancer.

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