P12.31.B A NOVEL ORGANOID MODEL RETAINING THE GLIOMA MICROENVIRONMENT FOR PERSONALIZED DRUG SCREENING AND THERAPEUTIC EVALUATION

Abstract BACKGROUND Gliomas are the most common malignant brain tumors, characterized by their aggressive nature and poor prognosis. Despite advancements in radiation and chemotherapy, the five-year survival rate for patients with glioma remains low. A significant challenge is the lack of experimental models that accurately replicate the tumor microenvironment and cellular heterogeneity of human gliomas, limiting the understanding of disease mechanisms and the development of effective therapies. MATERIAL AND METHODS Here, we present a novel approach to generate glioma organoids with a microenvironment (GlioME) from patient-derived glioma tissue. These organoids maintain the genetic and epigenetic characteristics of the primary tumor and preserve cell-to-cell interactions within the tumor microenvironment, including resident immune cells. Bulk RNA sequencing, whole exome sequencing, and DNA methylation analysis were used to confirm the molecular similarities between the organoids and primary glioma tissues. Immunofluorescence and flow cytometry were used to assess immune cell viability, comparing GlioME with floating glioma organoids. RESULTS Immunofluorescence, flow cytometry, and gene sequencing revealed that the organoids retained an immune microenvironment consistent with that of the original tumor. Unlike traditional cell lines and animal models, GlioMEs retain the immune microenvironment, allowing faster and more accurate immunotherapy screening. GlioME exhibited high responsiveness to chemotherapy and targeted therapy, demonstrating its potential for therapeutic screening applications. Notably, GlioME accurately predicted patient response to the recently approved MET inhibitor, vebreltinib. CONCLUSION In summary, our results demonstrate that GlioME can retain the parental glioma microenvironment in vitro and reliably test various therapeutic drugs. This organoid model provides a reliable in vitro platform for glioma microenvironment-related research and clinical drug screening.