Review Article: Does CAR-T Cell Therapy of Solid Cancer Need the Activation of an Innate Immune Response?

CAR-T cells have shown efficacious in the treatment of hematologic malignancies; however, their efficacy towards solid tumors is so far limited by multiple challenges such as poor T cell infiltration, limited persistence, and immune suppression within the tumor tissue. On the other hand, tumor regression, especially of metastases, can spontaneously occur, which has long intrigued the scientific community. Spontaneous regression is thought to be associated with a more global immune response, triggered through the activation of both innate and adaptive immune cells. The viewpoint discusses strategies for combining CAR-T cell therapy with approaches stimulating innate immune responses to facilitate clearance of solid tumors. Currently explored approaches include vaccination, cytokine-driven activation, contact-dependent immune cell interactions, and pharmacological co-treatment, all aiming at reshaping the local environment through recruiting and activating innate immune cells together with CAR-T cells to form a more comprehensive anti-tumor response.