title: [Gemcitabine augments major histocompatibility complex class I-related chain A expression in pancreatic cancer].
abstract: Major histocompatibility complex(MHC)class I related chain A( MICA) expressed on the cell surface of tumor cells functions as a ligand for natural killer group 2, member D (NKG2D), an important immunoreceptor expressed on natural killer ( NK ), CD8, and γδT cells. The interaction of MICA and NKG2D stimulates NK cell-mediated cytotoxicity. Gemcitabine (GEM), a key drug for pancreatic cancer treatment, stimulates the expression of cell surface MICA in tumor cells to enhance the cytotoxicity of NK cells. The combination of GEM and S-1 is used as a neoadjuvant chemotherapy (NAC) drug for pancreatic cancer in our department. We investigated the effect of GEM on pancreatic cancer. On immunohistochemistry, MICA expression was positive in 11 of 13 (85%) pancreatic ductal adenocarcinomas in the NAC group, and in 4 of 11 (36%) in the placebo control group. There was a greater proportion of NKG2D-positive cells in 5 random samples taken from both the NAC groups( 10 of 13, 77%) than in equivalent samples taken from the placebo control group( 3 of 11, 27%). In addition, CD16-positive cells were more prevalent among NK, CD8, and γδT cells in the NAC group( 9 of 13, 69%) than in the placebo control group( 3 of 11, 27%). Therefore, GEM may induce MICA expression on the surface of pancreatic cells and thus cause the accumulation of NKG2D and CD16-positive cells around tumors.
authors.affiliation: Dept. of Gastroenterological Surgery, Kanazawa University Hospital.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Shoji
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakanuma
authors.forename: Seisho
authors.initials: S
authors.lastname: Sakai
authors.forename: Isamu
authors.initials: I
authors.lastname: Makino
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Nakagawara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamura
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D003841:Deoxycytidine; D000093542:Gemcitabine