Naslov
Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells

Autori
Molon, Barbara ; Ugel, Stefano ; Del Pozzo, Federica ; Soldani, Cristina ; Zilio, Serena ; Avella, Debora ; De Palma, Antonella ; Mauri, PierLuigi ; Monegal, Ana ; Rescigno, Maria ; Savino Benedetta ; Colombo, Pierguiseppe ; Jonjić, Nives ; Pećanić, Sanja ; Lazzarato, Loretta ; Fruttero, Roberta ; Gasco, Alberto ; Bronte, Vincenzo ; Viola, Antonella

Izvornik
The Journal of experimental medicine (0022-1007) 208 (2011), 10; 1949-1962

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
chemokine nitration; intratumoral infiltration; antigen-specific T cells.

Sažetak
Tumor-promoted constraints negatively affect cytotoxic T lymphocyte (CTL) trafficking to the tumor core and, as a result, inhibit tumor killing. The production of reactive nitrogen species (RNS) within the tumor microenvironment has been reported in mouse and human cancers. We describe a novel RNS-dependent posttranslational modification of chemokines that has a profound impact on leukocyte recruitment to mouse and human tumors. Intratumoral RNS production induces CCL2 chemokine nitration and hinders T cell infiltration, resulting in the trapping of tumor-specific T cells in the stroma that surrounds cancer cells. Preconditioning of the tumor microenvironment with novel drugs that inhibit CCL2 modification facilitates CTL invasion of the tumor, suggesting that these drugs may be effective in cancer immunotherapy. Our results unveil an unexpected mechanism of tumor evasion and introduce new avenues for cancer immunotherapy.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA