Prolyl isomerase Pin1 sculpts the immune microenvironment of colorectal cancer

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.PMID:38199598 | DOI:10.1016/j.cellsig.2024.111041

Source: Cellular Signalling - January 10, 2024 Category: Cytology Authors: Yang Li Zhongnan Yuan Linlin Wang Jing Yang Pei Pu Yunting Le XianWei Chen Chongyang Wang Yating Gao Yi Liu Jialin Wang Xu Gao Yanze Li Hefei Wang Chaoxia Zou Source Type: research