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Gan To Kagaku Ryoho. 2012 Nov;39(12):1800-2.

[Human endoplasmic reticulum oxidoreductin 1-like α regulates immune response of cancer cells via modulation of major histocompatibility complex class I expression and oxidation].

[Article in Japanese]

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First Dept. of Surgery, Sapporo Medical University, Japan.


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.

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