title: [Human endoplasmic reticulum oxidoreductin 1-like α regulates immune response of cancer cells via modulation of major histocompatibility complex class I expression and oxidation].
abstract: The protein human endoplasmic reticulum oxidoreductin 1-like α(hERO1-L α) is a hypoxia-inducible endoplasmic reticulum resident oxidase that regulates the redox state of various proteins via protein disulfide isomerase. The major histocompatibility complex(MHC) class I molecule contains intramolecular disulfide bonds. hERO1-L α is expressed within normoxic cells at very low levels, but may be induced in hypoxic cells such as tumor cells in response to low oxygen availability. We therefore examined whether hERO1-L α affects the oxidation state and expression level of MHC class I in the colon cancer cell line SW480. We generated SW480 cells in which hERO1-L α was overexpressed or knocked down. The surface expression of MHC class I molecule was upregulated in the hERO1-L α-overexpressing SW480 cells and downregulated in the hERO1-L α-knockdown SW480 cells. Moreover, the oxidized form of MHC class I was increased in the hERO1-L α-overexpressing SW480 cells, and the hERO1-L α-knockdown SW480 cells exhibited an impaired response to cytotoxic T lymphocytes. These data suggest that hERO1-L α regulates immune response via modulation of MHC class I expression and oxidation, and that hERO1-L α may act as a new predictive factor for cancer immunotherapy.
authors.affiliation: First Dept. of Surgery, Sapporo Medical University, Japan.
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Kukita
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Oku-ya
authors.forename: Keita
authors.initials: K
authors.lastname: Saito
authors.forename: Goro
authors.initials: G
authors.lastname: Kutomi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D045744:Cell Line, Tumor; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; C405327:ERO1A protein, human; D010088:Oxidoreductases