Abstract A001: Microdevice Implantation for Immune Modulation and Drug Response Evaluation in Glioblastoma Patients

Abstract Glioblastoma (GBM) is the most aggressive and treatment-resistant primary brain tumor. Despite advancements in immunotherapies and targeted therapies, patient outcomes remain poor due to the complexity of the GBM tumor microenvironment. The spatial heterogeneity within GBM tumors leads to variable immune responses and drug efficacy, posing significant challenges for effective treatment. This study presents an innovative approach using implantable microdevices (IMDs) for localized drug delivery and real-time monitoring of immune modulation and therapeutic response in GBM patients. Preliminary findings from our pilot study using IMDs in GBM patients demonstrate their ability to generate spatially resolved data on drug responses. New data, collected within a three-day window post-implantation, revealed enhanced drug action and provided a deeper understanding of how the tumor microenvironment is reshaped. By integrating advanced spatial biology techniques—including CycIF, spatial transcriptomics, and spatial mass spectrometry—this approach offers new insights into how drugs affect the tumor microenvironment at both the cellular and molecular levels directly in the patient. We used CycIF to visualize how immune cells infiltrate the tumor and respond to various therapies, including immunomodulatory drugs like checkpoint inhibitors. At the transcriptional level, spatial transcriptomics provided high-resolution, spatially mapped gene expression profiles, revealing how different regions of the GBM tumor respond to drug exposure. By retrieving tissue from distinct drug-exposed zones, this technique allowed for the identification of gene expression patterns associated with drug efficacy, immune activation, and resistance mechanisms. Additionally, spatial mass spectrometry provided a powerful tool for mapping the molecular landscape of the GBM tumor microenvironment in response to drug treatments. By analyzing the spatial distribution of proteins, lipids, metabolites, and other molecular components, this technique revealed apoptotic regions in tumor cells as a result of localized drug exposure. This finding is consistent with IHC staining for apoptosis markers, such as cleaved caspase-3. The combination of implantable microdevices with spatial biology, spatial transcriptomics, and spatial mass spectrometry represents a groundbreaking advance in the study of immune modulation and drug response in GBM patients. Each of these spatial techniques contributes unique insights into the cellular and molecular dynamics within the tumor, enabling a more nuanced understanding of how immune cells and tumor cells interact in response to therapy. By providing real-time, spatially resolved data on therapeutic efficacy and resistance, this approach offers a powerful tool for optimizing personalized treatment strategies for GBM, despite the tumor’s heterogeneity. Citation Format: Vincenzo Tarallo, Oliver Jonas. Microdevice Implantation for Immune Modulation and Drug Response Evaluation in Glioblastoma Patients [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A001.