Abstract 4611: Leveraging organotypic brain slice models to enhance adoptive cellular therapies

Abstract Glioblastoma (GBM) is an incredibly aggressive and prevalent primary CNS tumor with dismal survival outcomes. GBM’s intra-tumor heterogeneity and lack of anti-tumor immune cell infiltration have proved to be formidable challenges to the development of effective therapies. These hurdles may be overcome by garnering a better understanding of the cell-cell interactions occurring within the tumor microenvironment (TME). Accounting for the complexity and the spatial orientation of the components within the TME may offer insight into the multitiered layers of immunosuppression capitalized on by GBM tumors, thus elucidating the factors responsible for poor response to therapy and uncovering potential therapeutic targets that may offer more favorable therapeutic results for immunotherapies. Current in vitro and in vivo models, however, sorely limit our ability to probe these distinct attributes while preserving the intricate nature of the TME. To bridge this gap, we have devised a novel organotypic brain slice culture (BSC) model using tumor-bearing C57BL/6J mice, allowing us to characterize the tumor milieu in situ. We have identified infiltration of myeloid-derived suppressor cells (MDSC) and microglia polarized to the M2 anti-inflammatory phenotype within the TME. Leveraging this platform, we sought to define further the factors contributing to the dynamic impacts of GBM immunosuppression, such as the tolerogenic response in dendritic cells (DC) upon interaction with the TME. We have demonstrated outcomes similar to those seen in vivo following the introduction of DCs to tumor-bearing BSCs, further supporting the physiological relevancy of this model, and have since worked to unravel elements responsible for this response. Citation Format: Alexandra Reid, Dan Jin, Bayli DiVita-Dean, Laura Falceto-Font, John Figg, Connor Francis, Catherine Flores. Leveraging organotypic brain slice models to enhance adoptive cellular therapies. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4611.