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Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells

Barbara Molon1, Stefano Ugel, Federica Del Pozzo

  • 1Istituto Oncologico Veneto, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Venetian Oncological Institute, 35128 Padua, Italy. barbara.molon@unipd.it

The Journal of Experimental Medicine
|September 21, 2011
PubMed

Insights

Tumor-produced reactive nitrogen species (RNS) modify chemokines, blocking cytotoxic T lymphocyte (CTL) entry into tumors. Inhibiting this modification enhances CTL infiltration, offering a new cancer immunotherapy strategy.

Area of Science:

  • Immunology
  • Oncology
  • Biochemistry

Background:

  • Tumor microenvironments impede cytotoxic T lymphocyte (CTL) trafficking, hindering anti-tumor immunity.
  • Reactive nitrogen species (RNS) are present in various human and mouse cancers.
  • Leukocyte recruitment to tumors is crucial for effective anti-tumor responses.

Purpose of the Study:

  • To investigate a novel RNS-dependent posttranslational modification of chemokines.
  • To understand the impact of this modification on T cell infiltration in tumors.
  • To explore therapeutic strategies targeting this mechanism for cancer immunotherapy.

Main Methods:

  • Analysis of chemokine modification in mouse and human tumor models.
  • Assessment of T cell infiltration and trafficking in response to RNS.
  • Evaluation of novel drugs designed to inhibit chemokine modification.

Main Results:

  • Intratumoral RNS production leads to CCL2 chemokine nitration.
  • CCL2 nitration impairs T cell infiltration, trapping them in the tumor stroma.
  • Inhibiting CCL2 modification with novel drugs promotes CTL invasion of tumors.

Conclusions:

  • RNS-mediated chemokine modification is an unexpected tumor evasion mechanism.
  • Targeting this modification pathway presents a promising strategy for cancer immunotherapy.
  • Novel drugs inhibiting CCL2 modification could enhance the efficacy of cancer treatments.

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