1. PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer
- Author
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Wanlong Tan, Ji-min Gao, Xiaojun Shi, Lijun Mo, Xinji Zhang, Jinlong Li, Hongfan Zhao, Zhiming Hu, and Xianghua Shi
- Subjects
Male ,0301 basic medicine ,Cancer Research ,T-Lymphocytes ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Population ,Cancer Vaccines ,B7-H1 Antigen ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cell Line, Tumor ,PD-L1 ,Animals ,Medicine ,education ,education.field_of_study ,biology ,business.industry ,Granulocyte-Macrophage Colony-Stimulating Factor ,Prostatic Neoplasms ,FOXP3 ,Immunotherapy ,Vaccine therapy ,Blockade ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Disease Progression ,biology.protein ,Cancer research ,Streptavidin ,business ,CD8 ,T-Lymphocytes, Cytotoxic - 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.
- Published
- 2017
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