Abstract P19: Profiling of Colorectal Cancer Tumor Microenvironment using Spatial Multi-Omics

Abstract Colorectal cancer (CRC) is the third most common cancer in the world. Within the tumor microenvironment (TME), cancer cells are surrounded by diverse cell types including cancer-associated fibroblasts (CAFs) and immune cells. These neighboring cells can have a profound effect on prognosis and disease progression by providing local signals that impact tumor growth and metastasis. Prior work in the lab has identified via single cell RNA sequencing novel subtypes of cancer epithelial cells and enrichment of specific CAFs within the CRC TME. However, the locations and signaling interactions of these cells within the tumors remain poorly understood due to the loss of spatial information. In this study, we adopt a multi-facet approach to try to understand the CRC TME by utilizing a combination of single cell RNA sequencing and spatial omics technology. We first comprehensively characterized all the major cell types present in the CRC TME using single cell RNA sequencing, and with the knowledge gained, we set out to investigate the spatial localization of these cell types of interests and their interactions within the tumor architecture using the 10x Xenium Analyzer and merFISH. From our data, we identified subtypes of tumor epithelial cells that are uniquely enriched in CRC patients and observed distinct spatial organization of these cells within colonic glands across patient subgroups. In addition, we observed an enrichment of CAFs and immune cell populations at the tumor invasive margin, often accompanying regions of tumor budding. Further study of these tumor epithelial, CAF and immune subtypes and their spatial interactions may reveal new insights into CRC tumor biology and assist in the development of targeted therapies for CRC. Citation Format: Bo Li, Grace Hui Ting Yeo, Ignasius Joanito, Vairavan Lakshmanan, Yurike Laurensia, Run Bing Han, Nirmala Arul Rayan, Kok Hao Chen, Kiat Hon Lim, Iain Bee Huat Tan, Shyam Prabhakar. Profiling of Colorectal Cancer Tumor Microenvironment using Spatial Multi-Omics abstract. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85 (15Suppl): Abstract nr P19.