Fig. 4

Radiotherapy amplifies the effectiveness of CAR-T cell therapy in combination treatments. (1,2) Radiation-induced IFN-γ triggers the secretion of chemokines such as CXCL9, CXCL10, and CXCL11, which help guide CAR-T cells to the tumor site. (3) Reducing barriers within the tumor microenvironment (TME), facilitates CAR-T cell infiltration. (4) Radiation also increases the expression of ICAM-1 and VCAM-1 on tumor blood vessels, further aiding CAR-T cell infiltration. (5) Radiotherapy shifts macrophages in the TME from the M2 to the M1 phenotype. (6) Additionally, radiation decreases the presence of tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC). (7) By increasing the expression of proinflammatory cytokines, radiation transforms the TME from an immunosuppressive “cold” state to a more immune-active “hot” state. (8) This enhances the function of infiltrating CAR-T cells and supports the expansion of CAR-T cells. This figure was generated using BioRender.com