Involvement of PD-L1-mediated tumor-intrinsic signaling and immune suppression in tumorigenic effect of α-tocopherol. (17th October 2021)

• Record Type: Journal Article
• Authors: Sun, Zhenou; Yin, Shutao; Zhao, Chong; Fan, Li hong; Hu, Hongbo
• Is Part Of: Carcinogenesis. Volume 43:Number 3(2022)
• Page Start: 243
• Page End: 253
• Publication Date: 2021-10-17
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgab096
• Languages: English
• ISSNs: 0143-3334

Abstract

Abstract: Numerous studies have shown that the different isoforms vitamin E have distinct activity on carcinogenesis. α-Tocopherol (α-T), the most abundant vitamin E in certain types of food and animal tissues, has demonstrated a cancer-promoting effect in a number of human clinical trials and pre-clinical studies, whereas the γ- and δ- forms of Tocopherols and Tocotrienols have exhibited significant anticancer effect in various pre-clinical studies. However, the mechanisms underlying the tumorigenic effect of α-T have not yet been fully understood. In the present study, we found that α-T was able to activate programmed death-ligand 1 (PD-L1)-mediated tumor-intrinsic signaling and immune suppression via JAK/STAT3-dependent transcriptional and ERK-dependent post-transcriptional mechanism. In line with PD-L1 induction, α-T treatment increased cancer cell viability in vitro and promoted tumor growth in LLC xenograft mouse model. The findings of the present study for the first time provided evidence that PD-L1-mediated tumor-intrinsic and immune escape mechanism contributed to the tumorigenic effect of α-T. Abstract : α-Tocopherol upregulates PD-L1 expression both in vitro and in vivo . α-Tocopherol activates PD-L1-mediated tumor-intrinsic signals and immune suppression. PD-L1 induction contributes to the carcinogenic effect of α-tocopherol. Graphical Abstract: