Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells (CROSBI ID 178625)
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Podaci o odgovornosti
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
engleski
Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells
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.
chemokine nitration; intratumoral infiltration; antigen-specific T cells.
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Podaci o izdanju
208 (10)
2011.
1949-1962
objavljeno
0022-1007
10.1084/jem.20101956
Povezanost rada
Temeljne medicinske znanosti