Abstract
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.