| Literature DB >> 36220073 |
Evgenii N Tcyganov1, Emilio Sanseviero2, Douglas Marvel1, Thomas Beer3, Hsin-Yao Tang3, Peter Hembach3, David W Speicher3, Qianfei Zhang2, Laxminarasimha R Donthireddy1, Ali Mostafa2, Sabina Tsyganova4, Vladimir Pisarev5, Terri Laufer4, Dmitriy Ignatov6, Soldano Ferrone7, Christiane Meyer8, Hélène Maby-El Hajjami8, Daniel E Speiser8, Sooner Altiok9, Scott Antonia10, Xiaowei Xu11, Wei Xu11, Cathy Zheng11, Lynn M Schuchter12, Ravi K Amaravadi12, Tara C Mitchell12, Giorgos C Karakousis13, Zhe Yuan14, Luis J Montaner1, Esteban Celis14, Dmitry I Gabrilovich15.
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.Entities:
Keywords: cancer immunotherapy; cytotoxic T cells; myeloid cells; peroxynitrite; tumor microenvironment; tumor-associated antigens
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Year: 2022 PMID： 36220073 PMCID： PMC9566605 DOI： 10.1016/j.ccell.2022.09.001
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 38.585