Spatially-resolved, multiplexed quantification of protein and mRNA distribution and abundance in colorectal cancer tumor microenvironment with multiple modalities of NanoString GeoMx Digital Spatial Profiler

• Published in: Journal of clinical oncology Vol. 37; no. 15_suppl; p. e14218
• Main Authors: Demirkan, Gokhan, Merritt, Chris, Hinerfeld, Douglas, Ong, Giang, Sorg, Kristina, Balasundaram, Gayathri, Dunaway, Dwayne, Geiss, Gary K, Beechem, Joseph M
• Format: Journal Article
• Language: English
• Published: 20.05.2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.15_suppl.e14218

Abstract only e14218 Background: Characterization of the spatial distribution and abundance of proteins and mRNAs with morphological context within tissues enables a better understanding of biological systems in many research areas, including immunology and oncology. However, it has proven difficult to perform such studies in a highly multiplexed manner. To address this unmet need, we have developed a novel optical-barcode based microscope and tissue-sampling platform designed to simultaneously analyze hundreds of proteins or mRNAs on a single FFPE section from distinct tissue spatial regions. Methods: Using colorectal cancer FFPE sections we spatially resolve protein and mRNA expression of immune-oncology targets and present a series of modalities and associated applications for the GeoMx Digital Spatial Profiler platform. Results: Microsatellite stable (MSS) or instable (MSI) colorectal tumors will be characterized to evaluate active and suppressive immune mechanisms in both immune dense regions and tumor versus stroma by utilizing segment profiling. Regions from the invasive margins and tumor centers will be investigated with contour profiling to define different immunosuppressive and activated immune phenotypes. Evaluation of tumor versus stroma will also identify pathways related to each compartment that are different between MSI and MSS tumors. These techniques can be used to discover drug mechanism of action or immune activation status, as well as to facilitate prediction of treatment response and disease progression or investigation of specific rare cell populations’ molecular profiles. Conclusions: This study will demonstrate multiplexed pathway-level protein and gene expression analysis from discrete regions within a colorectal tumor (tumor center and immune invasive margin), enabling systematic interrogation of immune activity in FFPE samples. Further studies could eventually lead to the identification of unique localized immune characteristics to guide combination therapeutic approaches.