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

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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+CD25hi 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.

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Acknowledgments

This work was supported in part by a grant from Compagnia di San Paolo entitled “Immunoterapia anti-tumorale: analisi d’efficacia dei principali protocolli tradizionali d’immunizzazione e validazione dell’efficacia terapeutica dell’inibizione dell’interleuchina 10 nel trattamento del melanoma” and in part by a PRIN grant from MIUR entitled “Immunoterapia anti-tumorale operata attraverso l’inibizione dei circuiti regolatori citochino-dipendenti”. We thank Prof. A. Bacigalupo, Centro Cellule Staminali e Terapie Cellulari, IRCSS Azienda Ospedaliera Universitaria-San Martino IST, for allowing us to work in the Facs sorting facility.

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The authors declare that they do not have conflict of interest.

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Correspondence to Gilberto Filaci.

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Alessia Parodi and Florinda Battaglia contributed equally to this work.

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Parodi, A., Battaglia, F., Kalli, F. et al. CD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes. Cancer Immunol Immunother 62, 851–862 (2013). https://doi.org/10.1007/s00262-013-1392-z

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