六烯酸
免疫系统
癌症研究
癌细胞
蛋白酶体
生物
PD-L1
癌症免疫疗法
癌症
泛素
化学
多不饱和脂肪酸
免疫疗法
脂肪酸
生物化学
细胞生物学
免疫学
基因
遗传学
作者
Hanxiong Zhang,H. S. Chen,Shutao Yin,Lihong Fan,Caiwei Jin,Melvin L.K. Chua,Hongbo Hu
标识
DOI:10.1016/j.jnutbio.2022.109186
摘要
PD-L1 interacts with its receptor PD-1 on T cells to negatively regulate T cell function, leading to cancer cell immune escape from the immune surveillance. Therefore, targeting PD-L1 is considered to be an attractive approach for cancer immunotherapy. In this study, we demonstrated for the first time that ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) reduced the expression of PD-L1 in cancer cells both in vitro and in vivo. Promotion of PD-L1 ubiquitin-proteasome degradation by DHA resulted in a decrease of PD-L1 expression, leading to reduction of PD-L1 and PD-1 interaction, and reversing PD-L1-mediated immune suppression, which in turn contributed to the inhibitory effect on tumor growth. Furtherly, DHA significantly reduced fatty acid synthase (FASN) expression in cancer cells, which inhibited the palmitoyltransferases DHHC5, promoting the CSN5-dependent PD-L1 degradation. Our present finding uncovered a novel mechanism involved in the anti-cancer activity of DHA, and implicated that DHA holds promising potential to be developed as a novel immune-enhancer for cancer treatment and prevention.
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