Abstract A110: Detailed resolution analysis reveals spatial heterogeneity of T cell distribution in the invasive margin of colorectal cancer liver metastases

Abstract

On a broader scale T cell density and localization in colorectal cancer liver metastases (CRC-LM) have prognostic and predictive implications, while T cell distribution at higher resolutions has not been fully investigated. As the invasive front of CRC-LM represents a clear border between malignant tissue and adjacent normal liver tissue, a detailed resolution analysis of T cell distribution in this region could be performed. Tissue areas of 1 square millimeter size from different patients were analyzed by high-throughput whole slide imaging technology, showing distinct density patterns of T cell localization in relation to the malignant tissue across the invasive margins. Unsupervised clustering revealed specific groups of patients with T cell aggregates limited to a given distance from the tumor. Furthermore, regions with T cells in close contact to the tumor usually had elevated T cell numbers further away from the tumor, whereas the intermediate area showed limited enrichment. There seems to be a distance of around 10 to 30 micrometer from the tumor where a decrease in T cells is common. Interestingly, 68 percent of distant T cells were identified to be in close contact with tumor-associated macrophages. Therefore, the spatial heterogeneity of T cell distribution in the invasive margin could be accounted for interactions with immunosuppressive cells, cell-matrix interactions or chemotactic fields potentially generated by tumor or endothelial cells, which is currently investigated. Whether the presence of the observed patterns has clinical importance and might change under therapy remains to be seen. In summary, this high resolution analysis of T cell distribution within the invasive front of CRC-LM reveals insights into the detailed localization of T cells and possible spatial immunosuppressive hurdles that need to be overcome by immunotherapies. The analysis of reversal of these spatial profiles could serve as a biomarker for successful therapies. Citation Format: Anna Berthel, Inka Zoernig, Meggy Suarez-Carmona, Christoph Kahlert, Fee Klupp, Alexis Ulrich, Juergen Weitz, Dirk Jaeger, Halama Niels. Detailed resolution analysis reveals spatial heterogeneity of T cell distribution in the invasive margin of colorectal cancer liver metastases [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A110.