CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade

CONSTANZA RODRIGUEZ

Bioxriv

Cold Spring Harbor Laboratory

Año: 2023

ackground Conventional CD4+ T (Tconv) lymphocytes play important roles in tumor immunity; however, their contribution to tumor elimination remains poorly understood.Methods Here we describe a subset of Tconv cells characterized by the expression of CD39. The phenotype, the effector function and transcriptional profile of tumor-infiltrating CD39+ Tconv lymphocytes from different mouse cancer models and breast cancer patients were studied by multiparametric flow cytometry and RNA sequencing. The impact of the in vivo CTLA-4 blockade on the tumor-infiltrating CD39+ Tconv population was assessed in mice grafted with the immunogenic MC38 colorectal tumor. Overall survival was evaluated in a cohort of patients from the TCGA consortium.Results In mouse cancer models, we observed that CD39+ Tconv cells accumulated in tumors as they grew but were absent in lymphoid organs. Compared to tumor CD39− counterparts, CD39+ Tconv cells exhibited a cytotoxic and exhausted signature at the transcr