Adolf Ismael Chatita, Almars Amany, Dharsee Nazima, Mselle Teddy, Akan Gokce, Nguma Irene Jeremiah, Nateri Abdolrahman S, Atalar Fatmahan
Mbeya College of Health and Allied Sciences, University of Dar es Salaam, Mbeya, P.O Box 608, Tanzania.
Cancer Genetics & Stem Cell Group, BioDiscovery Institute, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, NG7 2UH, UK.
Genes Dis. 2021 Jun 30;9(5):1220-1233. doi: 10.1016/j.gendis.2021.06.004. eCollection 2022 Sep.
The immune system plays an important role in protecting the body against malignancy. During cancer immunoediting, the immune system can recognize and keep checking the tumor cells by down-expression of some self-molecules or by increasing expression of some novel molecules. However, the microenvironment created in the course of cancer development hampers the immune ability to recognize and destroy the transforming cells. Human Leukocyte Antigen G (HLA-G) is emerging as immune checkpoint molecule produced more by cancer cells to weaken the immune response against them. HLA-G is a non-classical HLA class I molecule which is normally expressed in immune privileged tissues as a soluble or membrane-bound protein. locus is highly polymorphic in the non-coding 3' untranslated region (UTR) and in the 5' upstream regulatory region (5' URR). HLA-G expression is controlled by polymorphisms located in these regions, and several association studies between these polymorphic sites and disease predisposition, response to therapy, and/or HLA-G protein expression have been reported. Various polymorphisms are demonstrated to modulate its expression and this is increasingly finding more significance in cancer biology. This review focuses on the relevance of the gene and its polymorphisms in cancer development. We highlight population genetics of as evidence to espouse the need and importance of exploring potential utility of HLA-G in cancer diagnosis, prognosis and immunotherapy in the currently understudied African population.
免疫系统在保护机体抵御恶性肿瘤方面发挥着重要作用。在癌症免疫编辑过程中,免疫系统可通过下调某些自身分子的表达或上调某些新分子的表达来识别并持续监测肿瘤细胞。然而,癌症发展过程中形成的微环境会阻碍免疫系统识别和破坏转化细胞的能力。人类白细胞抗原G(HLA - G)正作为一种免疫检查点分子出现,癌细胞更多地产生该分子以削弱针对它们的免疫反应。HLA - G是一种非经典的I类HLA分子,通常作为可溶性或膜结合蛋白在免疫特惠组织中表达。其基因座在非编码3'非翻译区(UTR)和5'上游调控区(5' URR)高度多态。HLA - G的表达受这些区域多态性的控制,并且已经报道了这些多态性位点与疾病易感性、治疗反应和/或HLA - G蛋白表达之间的多项关联研究。各种多态性被证明可调节其表达,并且这在癌症生物学中越来越具有重要意义。本综述重点关注HLA - G基因及其多态性在癌症发展中的相关性。我们强调HLA - G的群体遗传学,以此作为支持在目前研究不足的非洲人群中探索HLA - G在癌症诊断、预后和免疫治疗中潜在效用的必要性和重要性的证据。