CD274 and neoplasm: CAR‐Ts targeting both PD‐L1 on TAMs and tumor antigens block immunosuppressive signals while activating anti‐tumor immunity.[101] Additionally, next‐generation CAR‐T cells engineered to secrete cytokines help reprogram the TME, overcoming barriers like hypoxia, ECM, and nutrient limitation.[102] Novel CAR‐T therapies targeting both tumor cells and TAMs offer promising strategies to overcome immunosuppressive barriers, but TAM plasticity and off‐tumor toxicity remain significant challenges.