Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination.

Immunogenic cell death (ICD) is a stress-driven form of regulated cell death (RCD) in which dying tumor cells' specific signaling pathways are activated to release damage-associated molecular patterns (DAMPs), leading to the robust anti-tumor immune response as well as a reversal of the tumor immune microenvironment from "cold" to "hot". Chimeric antigen receptor (CAR)-T cell therapy, as a landmark in anti-tumor immunotherapy, plays a formidable role in hematologic malignancies but falls short in solid tumors. The Gordian knot of CAR-T cells for solid tumors includes but is not limited to, tumor antigen heterogeneity or absence, physical and immune barriers of tumors. The combination of ICD induction therapy and CAR-T cell immunotherapy is expected to promote the intensive use of CAR-T cell in solid tumors. In this review, we summarize the characteristics of ICD, stress-responsive mechanism, and the synergistic effect of various ICD-based therapies with CAR-T cells to effectively improve anti-tumor capacity.