Does selenium affect the expression of programmed cell death protein and its ligand in colorectal cancer?

Introduction: Selenium has the protective role in many cancers, especially in colorectal cancer (CRC); in contrast, programmed cell death protein-1 and its ligand, PD-1/PD-L1, have suppressor effects on anti-tumor immune system responses in CRC and inhibition of these molecules is one of the important purposes in cancer therapy. Therefore, in this study, we aimed to assess the ability of selenium on PD-L1 and PD-1 modulation in the CRC.Description: Multiple electronic databases and conferences were searched up to 2020, to assess the relationship between selenium, PD-1, PD-L1, and CRC. Many studies showed the major role of the immune system in tumor genesis and treatment of CRC. Tumors cells can escape anti-tumor immune responses by overexpression PD-L1; hence the high expression of PD-L1/PD-1 was shown in a group of CRC, named immunogenic CRC. Currently targeting the PD-L1/PD-1 pathway is performed by anti-PD-L1/PD-1 antibodies for reinforcement of anti-tumor immune system responses. On the other hand, it was reported a relationship between selenium and CRC prevention, incidence and therapy. Selenium as an antioxidant micronutrient could neutralize reactive oxygen species, an inducer of PD-L1 expression, at the inflammatory status of cancers. Addition PD-L1/PD-1 expression could be induced by hypoxia-inducible factor 1α (HIF1α) which is inhibited by Selenium. Similarly, expression of PD-L1 and PD-1 are regulated by some transcription factors and miRNAs which are affected by selenium. Consequently, selenium might be an effective micronutrient for the regulation of PD-L1/PD-1 in CRC.Discussion and conclusion: In immunogenic CRC, PD-L1/PD-1 expression might be regulated by selenium micronutrient through its antioxidant and inhibitory properties for inactivation and inhibition of HIF1α, transcription factors and miRNAs. Accordingly, selenium could be used accompanied with other therapies to reduce the inhibitory effects of PD-1/PDL-1 and reinforce anti-tumor immune system responses.