Back to Search
Start Over
Hypoxia augments MHC class I antigen presentation via facilitation of ERO1-α-mediated oxidative folding in murine tumor cells.
- Source :
-
European journal of immunology [Eur J Immunol] 2016 Dec; Vol. 46 (12), pp. 2842-2851. Date of Electronic Publication: 2016 Oct 18. - Publication Year :
- 2016
-
Abstract
- 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-α plays an important role in the hypoxia-induced augmentation of MHC class I-peptide complex expression. ERO1-α 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.<br /> (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Animals
Antigen Presentation
Disease Models, Animal
Female
H-2 Antigens metabolism
Humans
Hypoxia therapy
Melanoma therapy
Melanoma, Experimental
Mice
Mice, Inbred C57BL
Mice, Transgenic
Oxidation-Reduction
Oxidoreductases
Protein Folding
T-Lymphocytes, Cytotoxic transplantation
Tumor Microenvironment
Glycoproteins metabolism
Hypoxia immunology
Immunotherapy methods
Melanoma immunology
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 46
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 27667124
- Full Text :
- https://doi.org/10.1002/eji.201646525