CD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes

Alessia Parodi, Florinda Battaglia, Francesca Kalli, Francesca Ferrera, Giuseppina Conteduca, Samuele Tardito, Silvia Stringara, Federico Ivaldi, Simone Negrini, Giacomo Borgonovo, Alchiede Simonato, Paolo Traverso, Giorgio Carmignani, Daniela Fenoglio, Gilberto Filaci

Research output: Contribution to journalArticle

Abstract

CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25hi Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25 hi Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+ Treg (both from peripheral blood and tumor microenvironment) suggesting that CD39-mediated inhibition constitutes a prevalent hallmark of their function. Collectively, these findings, unveiling a new mechanism of action for CD8+ Treg, provide new knowledge on intratumoral molecular pathways related to tumor immune escape, which could be exploited in the future for designing new biological tools for anticancer immune intervention.

Original languageEnglish
Pages (from-to)851-862
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume62
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • CD39
  • CD8+ Treg
  • Tolerance
  • Tumor immune escape

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

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  • Cite this

    Parodi, A., Battaglia, F., Kalli, F., Ferrera, F., Conteduca, G., Tardito, S., Stringara, S., Ivaldi, F., Negrini, S., Borgonovo, G., Simonato, A., Traverso, P., Carmignani, G., Fenoglio, D., & Filaci, G. (2013). CD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes. Cancer Immunology, Immunotherapy, 62(5), 851-862. https://doi.org/10.1007/s00262-013-1392-z