Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in...

Lack of pre-clinical models that simulate the complex TME and translate to human immunity is list as the top one challenge in the area of cancer immunotherapy development. While newly emerging organoid models play a crucial role in promoting the development of precision medicine in cancer immunotherapies. With the aid of experimental techniques and co-culture models of immuno-oncology, researchers have made progress in modeling tumor microenvironment (TME) with organoid-immune co-culture technologies to enhance the cellular complexity of the in vitro models, thus helping to improve existing immunotherapies, identify new immunotherapies and find reliable markers to predict the efficacy of immunotherapies for patients with cancer. In the review, we present an overview of the development of the different methods of three-dimensional (3D) patient-derived tumor organoids (PDTOs) modeling TME to study the interaction of tumor with cancer-associated fibroblasts (CAFs), lymphoid cells and myeloid immune cells. Besides, their methods and application in screening for efficacy of pharmacological immunotherapy and cellular immunotherapy in a personalized manner have also been summarized in the review. Moreover, we describe the applications of PDTOs modeling TME in specific cancer types and then summarize their contributions to the development of tumor immunity in different types of cancers. By centering on PDTOs' ability to capture individual tumor-immune biology, the review offers a comprehensive, personalized perspective of PDTO-immune co-culture models, making it a critical resource for researchers, clinicians, and drug developers aiming to advance precision immunotherapy.