Abstract 1602: Advancing personalized medicine using precision-cut tumor slices - assessing individual responses to immunotherapy in the tumor microenvironment

Abstract Immunotherapies have emerged as a promising pillar for cancer therapy. However, due to their reliance on the individual, complex and dynamic tumor microenvironment, treatment success remains limited to a subset of patients. A deeper understanding of the response of individual tumors and their heterogeneous microenvironment is essential to improve patient stratification and develop novel treatment approaches. This requires suitable model systems which allow tracking of the tumor microenvironment‘s (TME) response to immunotherapy. In this study, we combined patient-derived precision-cut tumor slices (PCTS) with multiplex immunofluorescence staining and cytokine analyses to trace the treatment response of different cell types in their native TME while preserving their location. PCTS derived from ovarian cancer, lung cancer and colorectal cancer tissue (n=13) were treated with OMTX305, an anti-FAP T-cell engaging bispecific antibody, for up to three days. A co-culture system integrating PCTS with autologous PBMCs was established to mimic the in vivo environment, and enable monitoring of immune cell activities. While treatment responses were patient-specific, determination of overall ATP levels of PCTS showed a significant decrease in viability after three days of treatment. Multiplex immunofluorescence stainings were performed to spatially analyze therapeutic effects, including T cell infiltration and distribution, T cell activation (Granzyme B) and cell death induction (Cleaved Caspase-3) in different cell types. T cells were significantly activated after treatment, and tumor slices showed significant cell death induction on the second day of treatment. Some patients showed T cell infiltration into FAP+ regions in response to treatment. Analysis of over 10 cytokines in the culture medium provides deeper insights into how the treatment induced immune cell activation. By integrating spatial biology and cytokine analysis with our PCTS platform, we can map the relationship between the tumor, stromal, and immune cell components within the TME, visualize inter-patient differences, and predict individual therapy responses to immunotherapy. This makes our platform a valuable tool for personalized cancer medicine. Citation Format: Julia Thiel, Jan Schlegel, Adrian Kneer, Sascha Dreher, Annelie Schäfer, Oliver Seifert, Katrin S. Kurz, Marc-H Dahlke, Georg Sauer, Gerhard Preissler, Laureano Simon, Myriam Fabre, Isabel Egaña, Roland Kontermann, Monilola Olayioye, German Ott, Walter E. Aulitzky, Thomas E. Mürdter, Matthias Schwab, Meng Dong. Advancing personalized medicine using precision-cut tumor slices - assessing individual responses to immunotherapy in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1602.