PD-1 blockade enhances the anti-tumor 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 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.

International journal of cancer. 2017 Dec 15 [Epub ahead of print]

Xiaojun Shi, Xinji Zhang, Jinlong Li, Lijun Mo, Hongfan Zhao, Yongtong Zhu, Zhiming Hu, Jimin Gao, Wanlong Tan

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Department of Urology, Shunde People's Hospital, Southern Medical University, Guangdong, China., Institute of Biotherapy, School of Biotechnology, Southern Medical University, Guangzhou, China., Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical University, Wenzhou, China.