title: MICA polymorphism: biology and importance in cancer.
abstract: The major histocompatibility complex class I polypeptide-related sequence A gene (MICA) encodes a membrane-bound protein acting as a ligand to stimulate an activating receptor, NKG2D, expressed on the surface of essentially all human natural killer (NK), γδ T and CD8(+) αβ T cells. MICA protein is absent from most cells but can be induced by infections and oncogenic transformation and is frequently expressed in epithelial tumors. Upon binding to MICA, NKG2D activates cytolytic responses of NK and γδ T cells against infected and tumor cells expressing MICA. Therefore, membrane-bound MICA acts as a signal during the early immune response against infection or spontaneously arising tumors. On the other hand, human tumor cells spontaneously release a soluble form of MICA, causing the downregulation of NKG2D and in turn severe impairment of the antitumor immune response of NK and CD8(+) T cells. This is considered to promote tumor immune evasion and also to compromise host resistance to infections. MICA is the most polymorphic non-classical class I gene. A possible association of MICA polymorphism with genetic predisposition to different cancer types has been investigated in candidate gene-based studies. Two genome-wide association studies have identified loci in MICA that influence susceptibility to cervical neoplasia and hepatitis C virus-induced hepatocellular carcinoma, respectively. Given the current level of interest in the field of MICA gene, we discuss the genetics and biology of the MICA gene and the role of its polymorphism in cancer. Gaps in our understanding and future research needs are also discussed.
authors.affiliation: Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala, Uppsala University, Biomedical Center, Box 815, 75108 Uppsala, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala, Uppsala University, Biomedical Center, Box 815, 75108 Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
mesh_terms: D055106:Genome-Wide Association Study; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A