Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells

作者：Barbara Molon, Stefano Ugel, Federica Del Pozzo, Cristiana Soldani, Serena Zilio, Debora Avella, Antonella De Palma, Pierluigi Mauri, Ana Monegal, María Rescigno, Benedetta Savino, Piergiuseppe Colombo, Nives Jonjić, Sanja Pečanić, Loretta Lazzarato, Roberta Fruttero, Alberto Gasco, Vincenzo Bronte, Antonella Viola · 发表于：The Journal of Experimental Medicine · 年份：2011 · DOI：10.1084/jem.20101956 · 被引用次数：650 · 研究领域：Immune Cell Function and Interaction、Chemokine receptors and signaling、Immune cells in cancer

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.