针脚1
免疫系统
癌症研究
脯氨酸异构酶
免疫检查点
FOXP3型
免疫疗法
肿瘤微环境
CD8型
肽基脯氨酰异构酶
生物
免疫学
化学
异构酶
生物化学
基因
作者
Yang Li,Zihao Yuan,Linlin Wang,Jiani Yang,Pei Yu Pu,Yunting Le,X. Chen,Chongyang Wang,Yating Gao,Yi Liu,Jialin Wang,Xu Gao,Yanze Li,Hefei Wang,Chaoxia Zou
标识
DOI:10.1016/j.cellsig.2024.111041
摘要
Pin1, a peptide prolyl cis-trans isomerase, is overexpressed and/or overactivated in many human malignancies. However, whether Pin1 regulates the immunosuppressive TME has not been well defined. In this study, we detected the effect of Pin1 on immune cells and immune checkpoint PD-L1 in the TME of CRC and explored the anti-tumor efficacy of Pin1 inhibitor ATRA combined with PD-1 antibody. We found that Pin1 facilitated the immunosuppressive TME by raising the proportion of myeloid-derived suppressor cells (MDSCs) and declining the percentage of CD8+ T cells and CD4+ T cells. Pin1 restrained PD-L1 protein expression in CRC cells and the effect was tempered by endoplasmic reticulum (ER) stress inducers. Mechanically, Pin1 overexpression decreased the stability of PD-L1 and promoted its degradation by mitigating ER stress. Silencing or inhibiting Pin1 promoted PD-L1 protein expression by inducing ER stress. Hence, Pin1 inhibitor ATRA enhanced the anti-tumor efficacy of PD-1 antibody in the CRC allograft by upregulating PD-L1. Our results reveal the critical and pleiotropic effects of Pin1 on managing the immune cells and immune checkpoint PD-L1 in the TME of CRC, providing a new promising candidate for combination with immunotherapy.
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