1. A new histone deacetylase inhibitor remodels the tumor microenvironment by deletion of polymorphonuclear myeloid-derived suppressor cells and sensitizes prostate cancer to immunotherapy
- Author
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Zude Chen, Xiaoshuang Yang, Zugen Chen, Minzhao Li, Wei Wang, Riwei Yang, Zuomin Wang, Yuxiang Ma, Yulong Xu, Shan Ao, Leqi Liang, Chao Cai, Changning Wang, Tuo Deng, Di Gu, Hongqing Zhou, and Guohua Zeng
- Subjects
HDAC inhibitor ,Epigenetics ,RM1 cell line ,MyC-CaP cell line ,Prostate carcinoma ,Anti-PD-1 ,Medicine - Abstract
Abstract Background Prostate cancer (PCa) is the most common malignancy diagnosed in men. Immune checkpoint blockade (ICB) alone showed disappointing results in PCa. It is partly due to the formation of immunosuppressive tumor microenvironment (TME) could not be reversed effectively by ICB alone. Methods We used PCa cell lines to evaluate the combined effects of CN133 and anti-PD-1 in the subcutaneous and osseous PCa mice models, as well as the underlying mechanisms. Results We found that CN133 could reduce the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and CN133 combination with anti-PD-1 could augment antitumor effects in the subcutaneous PCa of allograft models. However, anti-PD-1 combination with CN133 failed to elicit an anti-tumor response to the bone metastatic PCa mice. Mechanistically, CN133 could inhibit the infiltration of PMN-MDSCs in the TME of soft tissues by downregulation gene expression of PMN-MDSC recruitment but not change the gene expression involved in PMN-MDSC activation in the CN133 and anti-PD-1 co-treatment group relative to the anti-PD-1 alone in the bone metastatic mice model. Conclusions Taken together, our work firstly demonstrated that combination of CN133 with anti-PD-1 therapy may increase the therapeutic efficacy to PCa by reactivation of the positive immune microenvironment in the TME of soft tissue PCa.
- Published
- 2023
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