ID #962 Ex Vivo Functional Profiling of Post-Mortem Pediatric Brain Tumor Tissue through Gift from a Child

Abstract

Post-mortem pediatric brain tumor tissue provides a uniquely valuable yet rarely utilizable research resource, particularly for recurrent or end-stage disease where surgical access is impossible. Through the Gift from a Child program, we’ve received postmortem pediatric tumor specimens to characterize and evaluate their functional viability using our Screening Live Cancer Explants (SLiCE) platform, which supports uncultured, zero-passage patient tissue, including hard-to-maintain tumor subtypes. Because few preclinical models exist that can meaningfully utilize autopsy-derived tumors, where postmortem interval, ischemia, and tissue degradation pose major barriers, we first assessed whether these specimens retain viable cells upon arrival and evaluated how variables such as time-to-autopsy and shipping conditions influenced viability. We confirmed the presence of live tumor cells in received specimens and demonstrated that SLiCE supports the survival of the post-mortem tissue through our standard four-day assay endpoint comparably to non-post-mortem tissue. Simultaneously, we found no survival of samples plated in standard in vitro culture in several different high-quality medias. Following confirmation of tumor persistence, we evaluated therapeutic response to agents the patients had and had not previously received, observing differential tumor killing. We next characterized the cellular composition of each specimen prior to SLiCE using flow cytometry and identified both tumor and tumor-associated cell populations which persist through post-mortem tissue collection. Finally, we evaluated whether SLiCE could support active tumor–microenvironment signaling by quantifying soluble factors in transwell media over a four-day assay window, including baseline and dynamic changes in human IFN-γ, TGF-β, IL-10, and other cytokines. Together, these studies are signaling that post-mortem donations can be leveraged not only for genomic and transcriptomic profiling, but also for functional viability and TME biology within SLiCE, expanding the scientific impact of these extraordinary gifts from families and establishing a framework for incorporating post-mortem pediatric tumor tissue into precision modeling pipelines.