Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells

Barbara Molon, Stefano Ugel, Federica Del Pozzo, Cristiana Soldani, Serena Zilio, Debora Avella, Antonella De Palma, PierLuigi Mauri, Ana Monegal, Maria Rescigno, Benedetta Savino, Piergiuseppe Colombo, Nives Jonjic, Sanja Pecanic, Loretta Lazzarato, Roberta Fruttero, Alberto Gasco, Vincenzo Bronte, Antonella Viola

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1949-1962
Number of pages14
JournalJournal of Experimental Medicine
Volume208
Issue number10
DOIs
Publication statusPublished - Sep 26 2011

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Molon, B., Ugel, S., Del Pozzo, F., Soldani, C., Zilio, S., Avella, D., De Palma, A., Mauri, P., Monegal, A., Rescigno, M., Savino, B., Colombo, P., Jonjic, N., Pecanic, S., Lazzarato, L., Fruttero, R., Gasco, A., Bronte, V., & Viola, A. (2011). Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. Journal of Experimental Medicine, 208(10), 1949-1962. https://doi.org/10.1084/jem.20101956