Cell-based cancer immunotherapy: milestones, mechanistic insights, and emerging therapeutic directions

Cell-based immunotherapies have emerged as a transformative modality in modern cancer treatment, complementing conventional approaches such as surgery, chemotherapy, radiotherapy, and molecularly targeted therapies. This review provides an integrated and up-to-date synthesis of the rapidly evolving landscape of cellular immunotherapy, encompassing chimeric antigen receptor (CAR) T cells, T cell receptor (TCR)–engineered T cells, tumor-infiltrating lymphocytes (TILs), dendritic cell (DC) vaccines, natural killer (NK) cell–based therapies, and macrophage-directed strategies. We delineate the mechanistic foundations underlying each modality, summarize clinical outcomes across both hematologic malignancies and solid tumors, and critically evaluate therapeutic performance in the context of treatment-associated toxicities, resistance mechanisms, and barriers to durable response. Furthermore, we highlight emerging next-generation strategies designed to mitigate antigen escape, overcome immunosuppressive tumor microenvironments, and address challenges related to manufacturing, scalability, and accessibility. Collectively, these advances establish cell-based immunotherapies as a central component of precision oncology, with expanding potential to deliver durable and broadly accessible clinical benefit across diverse cancer types.