title: Sodium valproate sensitizes non-small lung cancer A549 cells to γδ T-cell-mediated killing through upregulating the expression of MICA.
abstract: Major histocompatibility complex (MHC) class I chain-related protein A (MICA) is involved in γδ T-cell recognition of target tumor cells. The aim of this study was to investigate the feasibility of utilization of sodium valproate (VPA), a histone deacetylase inhibitor, to sensitize non-small cell lung cancer A549 cells to γδ T-cell-mediated killing. VPA induced a dose-dependent increase in the mRNA and protein expression of MICA in A549 cells. γδ T cells showed cytotoxicity to A549 cells, which was increased by about 50% in the presence of VPA. The concomitant addition of MICA antibody significantly attenuated the VPA-mediated sensitization to γδ T-cell killing. VPA enhanced the cleavage of caspase-3 and caspase-9 in A549 cells cocultured with γδ T cells, and such enhancement was reversed by the MICA antibody. In conclusion, VPA sensitizes tumor cells to γδ T-cell-mediated cytotoxicity through the upregulation of MICA and may thus have benefits in improving γδ T-cell-based cancer immunotherapy.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, People's Republic of China. dxzdjy868@sina.com.
authors.forename: Xian-zhi
authors.initials: XZ
authors.lastname: Du
authors.forename: Qiong-ya
authors.initials: QY
authors.lastname: Li
authors.forename: Fa-wang
authors.initials: FW
authors.lastname: Du
authors.forename: Zheng-guang
authors.initials: ZG
authors.lastname: He
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014635:Valproic Acid / Q000008:administration & dosage*
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D014635:Valproic Acid
keywords: Apoptosis; Immunotherapy; MICA; Non-Small Lung Cancer; Sodium Valproate