CD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes.
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+CD25(hi) 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.
Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV n. 7, 16132, Genoa, Italy.
Alessia
A
Parodi
Florinda
F
Battaglia
Francesca
F
Kalli
Francesca
F
Ferrera
Giuseppina
G
Conteduca
Samuele
S
Tardito
Silvia
S
Stringara
Federico
F
Ivaldi
Simone
S
Negrini
Giacomo
G
Borgonovo
Alchiede
A
Simonato
Paolo
P
Traverso
Giorgio
G
Carmignani
Daniela
D
Fenoglio
Gilberto
G
Filaci
D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001081:Apyrase / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D049109:Cell Proliferation; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology*; D008856:Microscopy, Fluorescence; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
D015703:Antigens, CD; D000970:Antineoplastic Agents; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit; D001081:Apyrase; C067869:CD39 antigen