The breast cancer TME imposes multiple suppressive mechanisms that limit CAR-T cell efficacy, including cytokine-mediated inhibition (TGF-β, IL-10), immune checkpoint signaling (PD-L1, TIM-3, LAG-3), and stromal or metabolic barriers driven by cancer-associated fibroblasts (CAFs), ECM stiffness, and hypoxia-associated HIF-1α and YAP pathways [153–156]. The gene discussed is TGFB1; the disease is breast cancer.