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Rockefeller University Press, Journal of Experimental Medicine, 10(208), p. 1949-1962, 2011

DOI: 10.1084/jem.20101956

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Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells

Journal article published in 2011 by Barbara Molon, Stefano Ugel, Federica Del Pozzo, F. D. Pozzo, Cristiana Soldani, Serena Zilio, Debora Avella, Antonella De Palma ORCID, A. D. Palma, PierLuigi Mauri, Ana Monegal, Maria Rescigno ORCID, Benedetta Savino, Piergiuseppe Colombo ORCID, Nives Jonjic and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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.