Strategies for in situ reprogramming of tumor cells into antigen-presenting cells

Immune evasion is one of the fundamental characteristics of tumors, while immunotherapy has achieved significant success in cancer treatment in recent years. These therapies include immune checkpoint inhibitors, adoptive cell therapies [such as chimeric antigen receptor T cell therapy (CAR-T) and tumor-infiltrating lymphocytes (TIL)], cancer vaccines, and oncolytic viruses. Cell therapies have shown remarkable efficacy in various hematologic cancers, but their effect in solid tumors remains suboptimal, primarily due to the difficulty of infused immune cells in sufficiently infiltrating the tumor site. To address this challenge, researchers have explored strategies to reprogram tumor cells in situ within the tumor microenvironment into immune cells, so as to fully activate anti-tumor immune responses and overcome the limitations of conventional cell therapies that rely on in vitro cell expansion. This approach also offers the advantage of a weak immune rejection response. Currently, the target cells for in situ reprogramming include macrophages, granulocytes, dendritic cells (DCs), and T cells, among which dendritic cells, as classic antigen-presenting cells (APCs), play a central role in initiating immune responses and are key effectors in enhancing anti-tumor immunity. To date, two strategies for in situ reprogramming have been explored: one based on the ectopic expression of transcription factors and co-stimulatory molecules, and the other utilizing the co-expression of cytokines, both showing promising prospects for translational application.