Mechanistic insights and therapeutic innovation in immune-related adverse events

Immunotherapy has revolutionized oncology by harnessing the host immune system to combat malignancies, yet immune-related adverse events (irAEs) present formidable challenges to treatment sustainability and patient outcomes. This review systematically analyzes the mechanisms of irAEs induced by key immunotherapies, including immune checkpoint inhibitors (ICIs), chimeric antigen receptor T (CAR-T) cell therapy, cancer vaccines, and oncolytic viruses (OVs), with a focus on organ-specific manifestations. While current clinical management relies heavily on corticosteroids and immunosuppressive agents, prolonged use risks infections and diminished antitumor responses. Recent preclinical advances highlight innovative strategies to mitigate irAEs while preserving therapeutic activity, such as tumor-targeted drug delivery systems, cytokine pathway inhibitors, and certain indirect regulating protocols. Combinatorial approaches, including ICIs incorporated with chemotherapy or anti-angiogenic agents and traditional Chinese medicine interventions, have also demonstrated synergistic potential. Future directions emphasize elucidating molecular drivers of irAEs, developing predictive biomarkers, and refining targeted delivery technologies to balance efficacy and safety. This review underscores the critical role of interdisciplinary collaboration in advancing next-generation immunotherapies, offering actionable insights for optimizing clinical practice and translational research.