Abstract 6541: Spatial and longitudinal characterization of tumor microenvironment of peritoneal carcinomatosis: Nab-PIPAC phase IB trial

Abstract Peritoneal carcinomatosis is a major therapeutic challenge in gynecological and gastrointestinal malignancies, associated with poor quality of life and short survival. Little is known about the tumor microenvironment (TME) of peritoneal carcinomatosis resistant to chemotherapy. Using multiplexed immunohistochemistry (FoxP3, CD163, CD8, CD68, FAP and Cytokeratin) and sensitive T cell receptor (TCR) repertoire analysis, we investigated spatial and longitudinal changes of the TME of 54 biopsies collected from 18 patients with peritoneal carcinomatosis (six ovarian cancer, nine gastric cancer and three pancreatic cancer) treated in the Nab-PIPAC phase IB trial (repeated cisplatin and nab-paclitaxel by pressurized intraperitoneal aerosol chemotherapy [PIPAC]). Overall, tumors were cold with low T cell infiltration. There was high intra- and inter-patient heterogeneity of TCR repertoire and immune cell distribution, with different tumor patterns and TME compositions depending on the primary cancer. Ovarian and gastric cancers were enriched in CD163+ tumor-associated macrophages while pancreatic cancer was enriched in FAP+ cancer-associated fibroblasts and FoxP3+ regulatory T cells. TCR clonality was higher in ovarian cancer, as compared to oesogastric cancer, likely reflecting expansion of tumor reactive T cells. Focusing on ovarian cancer, hyperexpanded T cells were more abundant in the tumor core as compared to matched stroma. Our spatial and longitudinal study brings new insights into the TME of peritoneal carcinomatosis, with implications for the future design of precision medicine in this disease. Citation Format: Laura Grassi, Raphael Genolet, Valentine Du Bois, Manuela Undurraga, Thibaud Koessler, Jean-Christophe Tille, Antonella Diciola, Mariagrazia Di Marco, Noémie Lang, Nicolas Mach, remi Peanne, Eileen Zhao, Nawel Zouggari, Julie Terzic, Catherine Raimond, Patrick Petignat, Christian Toso, Stefan Monig, Martin Hübner, Frederic Ris, Alexandre Harari, Intidhar Labidi-Galy. Spatial and longitudinal characterization of tumor microenvironment of peritoneal carcinomatosis: Nab-PIPAC phase IB trial [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 6541.