Colorectal cancer interleukin-10 blockade scRNA-seq

Objective: PD-1 checkpoint inhibition and adoptive cellular therapy have limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We demonstrate that interleukin-10 (IL-10) blockade enhances endogenous T cell and chimeric antigen receptor T (CAR-T) cell anti-tumor function in CRLM slice cultures.Design: We created organotypic slice cultures from human CRLM (n = 38) and tested the anti-tumor effects of a neutralizing antibody against IL-10 (αIL-10). We evaluated slice cultures with single and multiplex immunohistochemistry, in situ hybridization, single cell RNA sequencing, and time-lapse fluorescent microscopy. In addition, we studied the effects of αIL-10 on carcinoembryonic antigen (CEA)-specific CAR-T cells exogenously administered to both human CRLM slice cultures and a CRLM murine model. Results: There was little effect of PD-1 blockade in CRLM slice cultures. In contrast, αIL-10 generated 1.8-fold increase in T cell-mediated carcinoma cell ...