From benchside avatars to bedside breakthroughs: Patient-derived organoids in the new era of cancer immunotherapy

The success of cancer immunotherapy is hampered by the lack of dynamic models that can predict patient-specific responses and guide the development of novel treatments. Static biomarkers, such as PD-L1 expression and tumor mutational burden, often fail to capture the complexity of the tumor-immune dialogue. Patient-derived tumor organoids (PDTOs) have emerged as a revolutionary ex vivo platform that bridges this gap. This review outlines the evolution of PDTOs from simple epithelial cultures to sophisticated, immune-competent "avatars" that faithfully recapitulate the patient's tumor microenvironment (TME). We critically discuss the key methodologies for reconstructing the TME, including "add-in" co-culture systems with diverse immune and stromal cells (e.g., T-cells, MDSCs, CAFs, neutrophils) and "all-in-one" approaches that preserve the native immune ecosystem. Furthermore, we highlight the expanding role of these advanced models beyond predicting checkpoint inhibitor efficacy. We showcase their groundbreaking applications as core development platforms for next-generation immunotherapies, including CAR-T cell therapy and the validation of personalized neoantigen-based vaccines. While acknowledging the significant translational challenges that remain, we conclude that immune-competent PDTOs represent an indispensable tool poised to accelerate the new era of precision immuno-oncology.