Peroxynitrite in the tumor microenvironment changes the profile of antigens allowing escape from cancer immunotherapy.
Details
Serval ID
serval:BIB_71E8BFD40E0A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Peroxynitrite in the tumor microenvironment changes the profile of antigens allowing escape from cancer immunotherapy.
Journal
Cancer cell
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Publication state
Published
Issued date
10/10/2022
Peer-reviewed
Oui
Volume
40
Number
10
Pages
1173-1189.e6
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Cancer immunotherapy often depends on recognition of peptide epitopes by cytotoxic T lymphocytes (CTLs). The tumor microenvironment (TME) is enriched for peroxynitrite (PNT), a potent oxidant produced by infiltrating myeloid cells and some tumor cells. We demonstrate that PNT alters the profile of MHC class I bound peptides presented on tumor cells. Only CTLs specific for PNT-resistant peptides have a strong antitumor effect in vivo, whereas CTLs specific for PNT-sensitive peptides are not effective. Therapeutic targeting of PNT in mice reduces resistance of tumor cells to CTLs. Melanoma patients with low PNT activity in their tumors demonstrate a better clinical response to immunotherapy than patients with high PNT activity. Our data suggest that intratumoral PNT activity should be considered for the design of neoantigen-based therapy and also may be an important immunotherapeutic target.
Keywords
Animals, Antigens, Neoplasm/metabolism, Epitopes, Histocompatibility Antigens Class I/metabolism, Immunotherapy, Melanoma/metabolism, Mice, Oxidants/metabolism, Peptides, Peroxynitrous Acid/metabolism, T-Lymphocytes, Cytotoxic, Tumor Microenvironment, cancer immunotherapy, cytotoxic T cells, myeloid cells, peroxynitrite, tumor microenvironment, tumor-associated antigens
Pubmed
Web of science
Create date
25/10/2022 14:39
Last modification date
07/03/2023 6:48