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

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

CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Año: 2017

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 ecto-nucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumorinfiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL-2 and expression of co-inhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore,exhausted CD39+CD8+ T cells inhibited IFN production by responder CD8+ 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 non-invaded lymph nodes and absent in peripheral blood. These