Major histocompatibility complex class I chain-related A and B molecules and their potential role in virus-associated cancers

Table 1 Major histocompatibility complex class I chain-related genes A/B alterations and immune evasion mechanisms in virus-associated cancers

Cancer type	Oncogenic virus	MICA/MICB alterations	Immune evasion mechanisms	Clinical implications
Cervical cancer	Human papillomavirus 16/18	Risk alleles: MICA*008:01, MICA*008:04, and MICA*018:01; protective alleles: MICA*002:01 and MICA*002:02; risk genotypes: MICA-129 Val/Val and Val/MICA-del; truncated MICA*008	Exosomal release of truncated MICA*008; reduce surface MICA/MICB; reduce NKG2D on NK cells	MICA polymorphisms associated with progression from cervical intraepithelial neoplasia to invasive cancer; reduce invasive risk linked to rs6938453
HCC	HBV/HCV	Reduce MICA/MICB expression; increase sMICA; rs2596542 TT genotype (risk); rs2596538 C/C genotype (increase HCV-HCC risk)	MICA shedding by ADAM10; UPR-mediated reduce MICA/MICB; sMICA-induced NKG2D reduce on NK/CD8+ T cells	Reduce MICA/MICB expression correlates with tumour aggressiveness and poor survival; increase serum sMICA predicts poor prognosis in HBV-HCC
Nasopharyngeal carcinoma	EBV	MICA rs2596542 AA genotype (risk); increase MICA protein expression in AA tumors; rs1051792 A allele (increase EBV titers)	EBV-miR-bamHI-A rightward transcript 7 inhibits transforming growth factor beta 1/cellular myelocytomatosis oncogene/MICA; latent membrane protein 2A-induced reduce surface MICA/MICB; UPR-protein disulfide isomerase inhibits proper MICA/MICB folding	AA genotype associated with increase EBV titers and MICA expression; NKG2D rs1049174 LNK/LNK genotype correlates with increase susceptibility
Gastric carcinoma	EBV	Variable MICA expression	Latent EBV infection with limited immune recognition	Dihydrotestosterone enhances MICA via nuclear factor-kappa B pathway in cell-line models, boosting NK/T cell cytotoxicity
Kaposi’s sarcoma	Kaposi’s sarcoma-associated herpesvirus	MICA*008 allele resistant to viral downregulation	K5 ubiquitination of MICA cytoplasmic tail; endocytic removal and intracellular sequestration of MICA; coordinated targeting of NKG2D (via MICA) and NKp80 (via activation-induced C-type lectin)	MICA*008 allele may influence host susceptibility due to resistance to K5-mediated downregulation

EBV: Epstein-Barr virus; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; MICA: Major histocompatibility complex class I chain-related genes A; NK cell: Natural killer cell; MICB: Major histocompatibility complex class I chain-related genes B; sMICA: Soluble major histocompatibility complex class I chain-related genes A.