Abstract 5565: Multiomic characterization of colorectal cancer using MICS technology reveals interaction of antigen presenting cancer associated fibroblasts and T cells

Abstract In solid tumors, the tumor microenvironment (TME) is composed of diverse cell types including cancer cells, immune cells, stromal cells, and other tissue specific cell types. The complex intercellular interactions that occur between these various cell populations determine cancer development and progression. Cancer-associated fibroblasts (CAFs) have been identified as key players in the TME, capable of promoting tumor cell growth and invasion, as well as manipulating immune responses. To better resolve potential subpopulations, spatial relationships, and signaling occurring between cell types within the TME, we performed same-section multiomic profiling of colorectal cancer (CRC) using the MACSima™ Imaging Cyclic Staining (MICS) technology. We combined a custom 40plex RNA panel with a panel of antibodies to characterize the drivers of tumorigenesis and the activation state of immune cells. FFPE CRC specimens were reviewed by a pathologist for clinical assessment and region of interest selection. Then, gene expression profiles were generated using RNAsky™ technology with each gene being detected via cyclic rounds of detection probe hybridization, image acquisition, and signal erasure. Subsequently, fluorescently labeled antibodies were applied to the same section following an equivalent acquisition process. Finally, multiomic clustering and cell population analyses were performed using MACS® iQ View software. The analysis revealed spatially separated subpopulations of CAFs. Functional characterization of cellular neighborhoods and the cell-to-cell interactions occurring within the TME showed that one of the CAF populations potentially promoted cancer cell growth while another subpopulation, resembling antigen-presenting CAFs (apCAFs), closely interacted with T cells in the TME. These findings will deepen our understanding of tumor progression in colorectal cancer and potentially other solid tumors. Citation Format: Emily Neil, Rebecca C. Hennessey, David Agorku, Dongju Park, Julia Femel, Michael DiBuono, Hanna Lafayette, Erica Lloyd, Hsinyi Lo, Alex Makrigiorgos, Shaina Lu, John Lee, Sameh Soliman, Dominic Mangiardi, Paurush Praveen, Philip Ströbel, Silvia Rüberg, Fabian Staubach, Ryan Hindman, Thomas Rothmann, Olaf Hardt, Hansueli Meyer, Tanya Wantenaar, Jinling Wang, Werner Müller, Robert Pinard, Andreas Bosio. Multiomic characterization of colorectal cancer using MICS technology reveals interaction of antigen presenting cancer associated fibroblasts and T cells abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5565.