Immune-Competent Tumor Organoid Models: Construction Strategies and Their Application in Predicting Immune Checkpoint...

The immune checkpoint blockade (ICB) has changed the way many solid tumors are treated; yet, only a minority of patients respond durably. The biomarkers that guide therapy (the PD-L1 expression, tumor mutational burden, and microsatellite status) read only fixed molecular features and miss the shifting tumor-immune exchange. Patient-derived tumor organoids reproduce the tumor epithelium and predict the chemotherapy responses, but, in their usual form, they omit the immune compartment on which the ICB acts. This review asks how immune-competent organoids can close that gap, and how well they predict the response. One idea organizes the field: how a model is built determines what it can predict. Two complementary construction routes have been developed. One preserves endogenous immunity through an air-liquid interface culture; the other rebuilds it by a co-culture with defined effector populations. Both now incorporate microenvironmental reconstruction and quantitative functional readouts. The most developed examples are in colorectal cancer, with breast cancer applications only beginning to appear. Evidence for the ICB response prediction, graded on a four-level scale, remains at the proof-of-concept stage. Organoid functional assays complement rather than replace molecular biomarkers. Their clinical translation requires progress on four fronts: standardized protocols, longer immune cell viability, spatial and multi-omic integration, and prospective paired validation.