Tumor immune organoids in immunotherapy resistance and drug screening

Tumor organoids represent a transformative tool in cancer research, as they retain the genetic and phenotypic features of parental tumors and accurately recapitulate their heterogeneity. However, one of the limitations of tumor organoids lies in the lack of immune and stromal cells in the tumor microenvironment (TME). To address this challenge, tumor immune organoids have been developed, which contain complex immune and stromal compartments beyond preserving tumor architecture. Tumor immune organoids show great potential for studying personalized immunotherapy responses and mechanisms of immunotherapy resistance. However, integrating the models into clinical practice remains challenging. In this Review, we outline currently available and rapidly evolving tumor immune organoids that recapitulate the TME and immunotherapy effects. These tumor immune organoids can be established by co-culturing traditional tumor organoids with stromal and immune cells, as well as preserving the TME using microfluidic and air-liquid interface (ALI) culture technologies. Additionally, we delineate the applications of tumor immune organoids for unravelling tumor-intrinsic and -extrinsic immunotherapy resistance mechanisms, predicting immunotherapy efficacy, and facilitating novel drug screening. Finally, we highlight the current challenges of organoid culture technology that need to be addressed for its broader applications, both in basic and translational cancer research. This review provides a theoretical foundation for future research on the application of tumor immune organoids to investigate immunotherapy resistance mechanisms and develop personalized immunotherapies. With continuous advancements, tumor immune organoids are expected to play an increasingly indispensable role in cancer immunotherapy, providing patients with more effective and tailored treatment options.