| First Author | Tcyganov EN | Year | 2022 |
| Journal | Cancer Cell | Volume | 40 |
| Issue | 10 | Pages | 1173-1189.e6 |
| PubMed ID | 36220073 | Mgi Jnum | J:355257 |
| Mgi Id | MGI:7366815 | Doi | 10.1016/j.ccell.2022.09.001 |
| Citation | Tcyganov EN, et al. (2022) Peroxynitrite in the tumor microenvironment changes the profile of antigens allowing escape from cancer immunotherapy. Cancer Cell 40(10):1173-1189.e6 |
| abstractText | 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. |
