Abstract
Cancer immunotherapy has transformed the therapeutic landscape of oncology by harnessing the body’s immune system to recognize and eradicate malignant cells. Over the past decade, immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)-T cell therapies, and personalized neoantigen vaccines have redefined treatment paradigms across multiple malignancies. The discovery of key regulatory pathways such as programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) has been instrumental in elucidating the mechanisms of immune tolerance and tumor immune evasion. The clinical success of monoclonal antibodies targeting these checkpoints such as pembrolizumab, nivolumab, and ipilimumab has led to durable responses in cancers once considered refractory to treatment. Recent innovations include the development of bispecific and trispecific antibodies, integration of CAR-T and CAR-NK cells for solid tumors, and multi-omics-guided precision immunotherapy. However, the rise in immune-related adverse events (irAEs), resistance mechanisms, and variability in patient response highlight the need for predictive biomarkers and personalized strategies. Emerging evidence suggests that the integration of artificial intelligence (AI), nanomedicine, and systems biology will optimize therapeutic efficacy and minimize toxicity. This review provides a comprehensive analysis of the mechanistic, translational, and clinical advances in cancer immunotherapy from 2019 to 2025, emphasizing novel strategies that are shaping the future of precision oncology.