Abstract 4944: Differential expression of complex immune biology in MSI and MSS colorectal tumor microenvironments using high-plex spatial resolution

Abstract

Abstract Spatial characterization of the tumor microenvironment (TME) including cancer cells, stroma and immune cells is essential for understanding tumor progression and discovering prognostic and predictive biomarkers. However, it has proven difficult to perform such studies in a highly multiplexed manner using limited sample quantity. GeoMx™ Digital Spatial Profiling (DSP) has been developed as an integrated research use platform for hi-plex spatial profiling of mRNA and protein using an optical-barcode read-out without the need for on-tissue molecular biology. In this study, we combined both bulk gene expression analysis using the NanoString PanCancer IO360™ panel and the spatial analysis of 40 proteins and 78 RNAs to characterize microsatellite stable (MSS) or instable (MSI) colorectal tumors to evaluate active and suppressive immune mechanisms in both immune dense regions and tumor versus stroma. Comparing colorectal tumors characterized by MSS, spatial analysis of RNA and protein expression by DSP was able to differentiate immune hot and cold regions of the tumors despite MSS status. Furthermore, comparison of immune-enriched hot-spots, measured by CD45 dense regions of interest, showed that MSS immune hot tumors had decreased macrophage and tumor proliferation markers compared to MSI immune hot tumors, elucidating potential therapeutic targets. Since there is a subset of patients with MSS colorectal cancer that still responds to immunotherapy, this suggests DSP could ultimately be used to identify unique spatial biology and immune characteristics that might further expand beyond MSS and MSI status and tradition gene signatures to help predict patients' response to mono- or combination therapy. Citation Format: Kit Fuhrman, Sarah Church, Daniel Zolligner, Jason Reeves, Doug Hinerfeld, Christina Bailey, Sarah Warren. Differential expression of complex immune biology in MSI and MSS colorectal tumor microenvironments using high-plex spatial resolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4944.