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
Author(s)
Tcyganov E.N., Sanseviero E., Marvel D., Beer T., Tang H.Y., Hembach P., Speicher D.W., Zhang Q., Donthireddy L.R., Mostafa A., Tsyganova S., Pisarev V., Laufer T., Ignatov D., Ferrone S., Meyer C., Maby-El Hajjami H., Speiser D.E., Altiok S., Antonia S., Xu X., Xu W., Zheng C., Schuchter L.M., Amaravadi R.K., Mitchell T.C., Karakousis G.C., Yuan Z., Montaner L.J., Celis E., Gabrilovich D.I.
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
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
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