The Extra‐Tumoral Vaccine Effects of Apoptotic Bodies in the Advancement of Cancer Treatment

Abstract The induction of apoptosis in tumor cells is a common target for the development of anti‐tumor therapies; however, these therapies still leave patients at increased risk of disease recurrence. For example, apoptotic tumor cells can promote tumor growth and immune evasion via the secretion of metabolites, apoptotic extracellular vesicles, and induction of pro‐tumorigenic macrophages. This paradox of apoptosis induction and the pro‐tumorigenic effects of tumor cell apoptosis has begged the question of whether apoptosis is a suitable cancer therapy, and led to further explorations into other immunogenic cell death‐based approaches. However, these strategies still face multiple challenges, the most critical of which is the tumor microenvironment. Contrary to the promotion of immune tolerance mediated by apoptotic tumor cells, apoptotic bodies with enriched tumor‐related antigens have demonstrated great immunogenic potential, as evidenced by their ability to initiate systemic T‐cell immune responses. These characteristics indicate that apoptotic body‐based therapies could be ideal “in situ” extra‐tumoral tumor vaccine candidates for the treatment of cancers, and further address the current issues with apoptosis‐based or immunotherapy treatments. Although not yet tested clinically, apoptotic body‐based vaccines have the potential to better treatment strategies and patient outcomes in the future.