Torabi, ShukoofehYekzaman, ElhamTaherkhani, SoroushTalachi, NeginKhoshravesh, RoyaKhosravi, ArezooVosough, Massoud2026-02-152026-02-1520251478-811X10.1186/s12964-025-02632-y2-s2.0-105029076344https://doi.org/10.1186/s12964-025-02632-yhttps://hdl.handle.net/20.500.14517/8752Solid tumors remain difficult to treat due to antigen heterogeneity, physical barriers that limit immune-cell trafficking, and a profoundly immunosuppressive tumor microenvironment (TME). Over the past decade, cancer immunotherapy advanced considerably through innovative strategies, including macrophage reprogramming and CAR-macrophages, dendritic-cell (DC) vaccines, natural killer (NK) and natural killer T (NKT) cell approaches, tumor-infiltrating lymphocyte (TIL) therapy, TCR-engineered and CAR-T cells, emerging B-cell engineering, and cell-derived extracellular vesicles (EVs). Here we summarize how each modality interacts with the TME, highlight key clinical milestones (e.g., FDA approval of a TIL product for melanoma in 2024), and outline bioengineering strategies-multi-antigen targeting, cytokine armoring, trafficking cues, and safety switches-that aim to overcome resistance and toxicity. We also review EV-based, cell-free strategies that retain tumor specificity with potentially improved safety and manufacturability. Finally, we discuss remaining barriers-standardized manufacturing, on-target/off-tumor effects, limited persistence-and propose rational combinations with checkpoint blockade, radiotherapy, and targeted agents. This overview positions immune cell-based therapy as a rapidly maturing, transformative approach for solid tumors.eninfo:eu-repo/semantics/openAccessSolid TumorCell TherapyImmune TherapyExtracellular VesiclesTmeArticle