PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer.

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.

• Authors: Xiaojun Shi, Xinji Zhang, Jinlong Li, Hongfan Zhao, Lijun Mo, Xianghua Shi, Zhiming Hu, Jimin Gao, Wanlong Tan
• Journal: Cancer letters (Cancer Lett) Vol. 406 Pg. 27-35 (10 10 2017) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 28797844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• B7-H1 Antigen
• Cancer Vaccines
• Cd274 protein, mouse
• Pdcd1 protein, mouse
• Programmed Cell Death 1 Receptor
• Granulocyte-Macrophage Colony-Stimulating Factor
• Streptavidin

Topics

• Animals
• B7-H1 Antigen (antagonists & inhibitors)
• Cancer Vaccines (immunology, therapeutic use)
• Cell Line, Tumor
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Programmed Cell Death 1 Receptor (antagonists & inhibitors)
• Prostatic Neoplasms (chemistry, immunology, therapy)
• Streptavidin (chemistry)
• T-Lymphocytes (immunology)
• T-Lymphocytes, Cytotoxic