Acquired resistance to immunotherapy in solid tumors

Acquired resistance to immunotherapy (ARI) is a major challenge in solid tumors, limiting long-term success in up to 65% of patients who initially respond to immunotherapy. Defining ARI clinically remains complex, but ongoing efforts aim to establish standardized criteria. This review describes recent insights into ARI, revealing complex mechanisms involving both tumor-intrinsic mechanisms – such as antigen loss and presentation defects, interferon γ (IFNγ) insensitivity, tumor-mediated T cell exclusion, and metabolic reprogramming – as well as extrinsic factors such as inhibitory molecule upregulation, immunosuppressive cells, extracellular matrix (ECM) remodeling, and dysbiotic microbiota. Understanding the development of ARI is crucial for prevention and effective interventions. The integration of innovative strategies and translational research on appropriately collected samples is key to overcoming ARI and ensuring durable benefits for patients.