مقالات پذیرفته شده در سومین کنگره بین المللی زیست پزشکی
Zinc and PD-L1 in Immunogenic Colorectal Cancer
Zinc and PD-L1 in Immunogenic Colorectal Cancer
Samane Mohamadzade,1,*Mohammad Hasan Emami,2
1. Poursina Hakim Digestive Disease Research Center, Isfahan University, Isfahan, Iran 2. Poursina Hakim Digestive Disease Research Center, Isfahan University, Isfahan, Iran
Introduction: The role of zinc in cancers has been reported in several studies; on the other hand, PD-L1/ PD-1 as an immune checkpoint pathway inhibit antitumor responses in colorectal cancer (CRC). Mismatch repair-deficient (MMR-d) CRC, by highly expression of PD-L1 could be define as the immunogenic CRC. The aim of this study was to investigate a relationship between zinc and PD-L1 in immunogenic CRC.
Methods: Multiple electronic databases and conference were searched up to 2019, for investigating the relation between zinc and PD-L1 in CRC.
Results: Epidemiological studies have represented an association between zinc level and the prevalence of cancers. Additionally, the immune system is predominantly sensitive to variations of this ion; Zinc ions induce the cytotoxic T cells and diminished zinc levels disturb the balances of Th1 to Th2 cells and reduce count of T cells. This ion, as the part of some regulatory proteins such as transcription factors and zinc fingers, regulates expression of genes related with angiogenesis, metastasis, cell proliferation, apoptosis, and tumor formation.
On the other hand, the immune system has the major role in tumor genesis and treatment of CRC. Tumors can escape immune response by different mechanisms including up-regulation of the immune-inhibitory molecules like ligands of co-inhibitory immune checkpoint receptors, e.g. PD-L1. High expression of PD-L1 was shown in CRC.
Mismatch repair-deficient (MMR-d) CRC, as an immunogenic type of CRC, has high mutations and neo-antigens, which has potential to be recognized by the immune system. The amount of PD-L1 expressing tumors were significantly high in MMR-d CRC.
It was shown that inefficient enzymatic DNA repair mechanisms are associated with zinc deficiency and they could increase risk of cancer initiation and progression. Accordingly, zinc deficiency may be one of the important causes of MMR-d CRC.
In addition, the anti-cancer effect of zinc is most often associated with its antioxidant properties. However, reactive oxygen species, ROS, induces PD-L1 expression, at the inflammatory status of cancers; therefore, deficient zinc antioxidant properties for neutralizing ROS, may be the inducer of PD-L1 expression on tumor cells in CRC.
Conclusion: In immunologic CRC, inefficient enzymatic DNA repair mechanisms and PD-L1 expression might be related to zinc deficiency. It may be prevented using supplementation of zinc, by retrieval of enzymatic DNA repair mechanisms and reduction of PD-L1 expression.