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Peroxynitrite in tumor microenvironment changes the profile of peptide antigens allowing escape from cancer immunotherapyстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Tcyganov E.N., Marvel D., Beer T.E., Tang H.Y., Hembach P., Speicher D., Donthireddy L.R., Tcyganova S., Laufer T., Pisarev V.M., Ignatov D., Ferrone S., Meyer C., Hajami H.Maby-El, Speiser D.E., Altiok S., Antonia S.J., Xu X., Xu W., Zheng C., Schuchter L.M., Amaravadi R.K., Mitchell T., Karakousis G., Celis E., Gabrilovich D.I.
- Журнал: Cancer Cell
- Том: 40
- Номер: 10
- Год издания: 2022
- Издательство: Cell Press
- Местоположение издательства: United States
- Первая страница: 1173
- Последняя страница: 1189
- DOI: 10.1016/j.ccell.2022.09.001
- Аннотация: 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.
- Добавил в систему: Писарев Владимир Митрофанович