Reconstructing the immune microenvironment in brain tumors: the role of organoid platforms in immunotherapy development

Brain tumors remain poorly responsive to current immunotherapies. This resistance is largely attributed to an immunosuppressive immune microenvironment characterized by multiple features. However, conventional preclinical models often fail to recapitulate the dynamic interactions among tumor cells, immune components, and the brain tissue environment, limiting both mechanistic investigations and translational immunotherapy development. This review focuses on recent advances in organoid platforms for modeling the brain tumor immune microenvironment and their emerging roles in immunotherapy research. We discuss current strategies for establishing brain tumor organoids with immune components, and highlight how these models enable functional analysis of immune infiltration, local effector activity and immunosuppressive regulation. In addition, we summarize the translational applications of these platforms in brain tumor immunotherapy, including treatment response evaluation, identification of major resistance patterns, and preclinical testing of novel strategies. Organoid platforms provide a promising tool for studying brain tumor immunology and advancing immunotherapy research. With further improvements in model complexity, standardization, and clinical relevance, they may help bridge mechanistic insights and translational applications in brain tumors.