Emerging Advances in Solid Tumor Immunotherapy: A Comparative Review of CAR-T, CAR-NK, CAR-M, and TIL Therapies

Solid tumors pose persistent challenges to cellular immunotherapy due to an immuno-suppressive tumor microenvironment and antigenic heterogeneity. While chimeric antigen receptor T cell (CAR-T) therapy has demonstrated remarkable success in hematologic malignancies, its effectiveness in solid tumors remains hindered by limited tumor infiltration, antigen escape, and immune evasion. To overcome these barriers, next-generation strategies—such as CARengineered natural killer (CAR-NK) cells, CAR-macrophages (CAR-M), and tumor-infiltrating lymphocyte (TIL) therapies—have emerged as innovative approaches. Each of these platforms offers distinct advantages: CAR-T cells provide potent cytotoxicity; CAR-NK cells leverage innate immune responses with a lower risk of graft-versus-host disease; CAR-M actively reshape the tumor microenvironment; and TILs enhance the persistence and infiltration of effector lymphocytes. Ongoing clinical trials underscore the rapid evolution of the therapeutic landscape, propelled by advancements in cell engineering and a deeper understanding of tumor immunobiology. While challenges remain, these emerging therapies represent promising avenues for achieving durable responses in solid tumors.