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.
Cancer letters. 2017 Aug 07 [Epub ahead of print]
Xiaojun Shi, Xinji Zhang, Jinlong Li, Hongfan Zhao, Lijun Mo, Xianghua Shi, 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; Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Institute of Biotherapy, School of Bitechnology, Southern Medical University, Guangzhou, China., Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical, College, Wenzhou, China., Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: .