CD39 expression defines cell exhaustion in tumor-infiltrating CD8+ T cells

CANALE, FERNANDO P.; RAMELLO, MARÍA C.; NÚÑEZ, NICOLÁS; FURLAN, CINTIA L. ARAUJO; BOSSIO, SABRINA N.; SERRÁN, MELISA GOROSITO; BOARI, JIMENA TOSELLO; DEL CASTILLO, ANDRÉS; LEDESMA, MARTA; SEDLIK, CHRISTINE; PIAGGIO, ELIANE; GRUPPI, ADRIANA; RODRÍGUEZ, EVA V. ACOSTA; MONTES, CAROLINA L.

CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Año: 2018 vol. 78 p. 115 - 115

0008-5472

he ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ectonucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39+CD8+ T cells inhibited IFNg production by responderCD8+ T cells. In specimens from breast cancer and melanoma patients, CD39+CD8+ T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhi