Patient-derived organoids (PDOs): a novel preclinical platform to overcome challenges in cancer immunotherapy

Cancer immunotherapy has revolutionized oncology but faces significant challenges including low response rates and lack of effective preclinical models. This review elucidates how patient-derived organoids (PDOs) are emerging as a transformative platform to address these hurdles. We detail sophisticated immuno-PDO (iPDO) models, categorized into reconstituted systems (co-culturing PDOs with exogenous immune cells) and native systems (preserving endogenous tumor microenvironment via Air-Liquid Interface or Patient-Derived Organotypic Tumor Spheroids). A problem-solution framework demonstrates how iPDOs: (1) deconvolute the immunosuppressive TME; (2) function as “living biomarkers” for predicting clinical responses; (3) unravel resistance mechanisms via multi-omics; and (4) empower high-throughput screening for personalized combination therapies. Integration with bioengineering, multi-omics, and AI heralds a new era in precision immuno-oncology, holding immense promise for deciphering resistance and improving clinical outcomes.