CSF1-CAR Specifically Targets CSF1R+ Pancreatic Cancer Cells and Tumor-Associated Macrophages.

Abstract

Summary: A highly suppressive tumor immune microenvironment and nonspecific target endow malignant tumors with CAR-T cells. CSF1R is highly expressed on pancreatic cancer tissues compares with normal tissues in GEPIA database and M2 macrophages mainly contributing to the suppressive tumor microenvironment (TME), suggesting that CSF1R is a suitable antigen. CSF1 is the natural ligand of CSF1R, so we constructed a CSF1-CAR and tested its cytotoxic effect on tumor cells and macrophages in vitro. Our results demonstrated that CSF1-CAR-T cells can lyse tumor cells dependent on CSF1R expression. Meanwhile, CSF1-CAR-T also lyse CSF1R+ M2 macrophages, suggesting that CSF1-CAR-T cells play a role in eliminating tumor cells and remodeling the TME.