GPR65 Inactivation in Tumor Cells Drives Antigen-Independent CAR T-cell Resistance via Macrophage Remodeling

The study identifies GPR65 as an important determinant of B-cell acute lymphoblastic leukemia response to CAR T-cell therapy. Notably, GPR65 absence signals CAR T resistance. By emphasizing the therapeutic potential of targeting VEGFA or host macrophages, our study identifies routes to optimize CAR T-cell therapy outcomes in hematologic malignancies via tumor microenvironment manipulation.