Immunogenic cell death in cold tumors: transforming immune-excluded tumors into immunotherapy-sensitive lesions

Immunogenic cell death (ICD) is a distinct mode of regulated cell death capable of activating adaptive immune responses against tumor antigens, offering great promise for cancer immunotherapy. However, immune-excluded or "cold" tumors, characterized by poor immune infiltration and limited responsiveness to conventional immunotherapies, remain a major clinical challenge. ICD induction has emerged as a compelling strategy to convert these immunologically inert tumors into immunotherapy-sensitive, immune-active ("hot") lesions by promoting dendritic cell activation, antigen presentation, and cytotoxic T-cell infiltration. This mini-review article highlights the potential of ICD-based therapeutic interventions, such as chemotherapy, radiotherapy, phototherapy, and nanoparticle-mediated delivery systems, to reprogram the immunosuppressive tumor microenvironment. By effectively converting cold tumors into immunologically responsive entities, ICD-centric approaches may significantly enhance the clinical efficacy of existing immunotherapies, highlighting the need for further translational research and personalized treatment strategies.