Hypoxia augments MHC class I antigen presentation via facilitation of ERO1‐α‐mediated oxidative folding in murine tumor cells

• DOI: 10.1002/eji.201646525
• Publication Date: 2016-09-26T08:52:38Z
• Authors: Toshimitsu Kajiwara; Tsutomu Tanaka; Kazuharu Kukita; Goro Kutomi; Keita Saito; Koichi Okuya; Akari Takaya; Vitaly Kochin; Takayuki Kanaseki; Tomohide Tsukahara; Yoshihiko Hirohashi; Toshihiko Torigoe; Koichi Hirata; Noriyuki Sato; Yasuaki Tamura
• Keywords: Cancer Immunotherapy; MHC restriction

To establish an effective cancer immunotherapy, it is crucial that cells present a cancer-specific antigen in hypoxic area, hallmark of the tumor microenvironment. Here, we show impact hypoxia on MHC class I presentation vitro and vivo murine tumors. Activation antigen-specific CTLs by had been pre-incubated under condition was enhanced compared with normoxia. Cell surface expression I-peptide complex increased hypoxia, thereby leading to higher susceptibility specific CTLs. We hypoxia-inducible ER-resident oxidase ERO1-α plays important role hypoxia-induced augmentation expression. facilitated oxidative folding heavy chains, resulting cell conditions. These results suggest since augmented microenvironment, strategies for inhibiting function regulatory T myeloid-derived suppressor and/or immunotherapy immune checkpoint inhibitors are promising improving immunotherapy.