| First Author | Kajiwara T | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 12 | Pages | 2842-2851 |
| PubMed ID | 27667124 | Mgi Jnum | J:246486 |
| Mgi Id | MGI:5922766 | Doi | 10.1002/eji.201646525 |
| Citation | Kajiwara T, et al. (2016) Hypoxia augments MHC class I antigen presentation via facilitation of ERO1-alpha-mediated oxidative folding in murine tumor cells. Eur J Immunol 46(12):2842-2851 |
| abstractText | To establish an effective cancer immunotherapy, it is crucial that cancer cells present a cancer-specific antigen in a hypoxic area, a hallmark of the tumor microenvironment. Here, we show the impact of hypoxia on MHC class I antigen presentation in vitro and in vivo in murine tumors. Activation of antigen-specific CTLs by tumor cells that had been pre-incubated under a condition of hypoxia was enhanced compared with that by tumor cells pre-incubated under a condition of normoxia. Cell surface expression of MHC class I-peptide complex on the tumor cells was increased under a condition of hypoxia, thereby leading to higher susceptibility to specific CTLs. We show that the hypoxia-inducible ER-resident oxidase ERO1-alpha plays an important role in the hypoxia-induced augmentation of MHC class I-peptide complex expression. ERO1-alpha facilitated oxidative folding of MHC class I heavy chains, thereby resulting in the augmentation of cell surface expression of MHC class I-peptide complex under hypoxic conditions. These results suggest that since the expression of MHC class I-peptide complex is augmented in a hypoxic tumor microenvironment, strategies for inhibiting the function of regulatory T cells and myeloid-derived suppressor cells and/or immunotherapy with immune checkpoint inhibitors are promising for improving cancer immunotherapy. |
