Abstract 5148: Interrogating immuno-oncological interactions in the tumor microenvironment

Abstract Single-cell RNA sequencing is a powerful and innovative tool for assessing individual cancer prognoses and outcomes; however, the process of generating this data typically destroys the spatial complexity of the tumor microenvironment. Understanding the spatial complexities within cancer provides crucial information for evaluating individual tumor development and progression. Vizgen’s MERSCOPETM Platform, built on Multiplexed Error-Robust Fluorescence in situ Hybridization (MERFISH) technology, enables the direct profiling of the spatial organization of intact tissue with subcellular resolution. Here, we present a Pan-Cancer approach to demonstrate the MERSCOPE’s ability to characterize breast, colon, prostate, ovarian, lung, and skin cancers from human clinical samples. Specifically, using a 500-gene panel to assess the canonical signaling pathways of cancer, cancer type-specific genes, select immune genes, proto-oncogenes, and tumor-suppressor genes, we show that the MERSCOPE was able to spatially profile gene expression across multiple tumor types. We utilized the Vizgen Cell Boundary Stain kit to generate a molecular and cellular atlas of individual patient tumors by clustering cells based on gene expression and mapping their spatial organization. To gather insight into immuno-oncological interactions and their effect on gene expression across these tumor types, we performed a neighborhood analysis to determine how proximity to immune cells altered gene expression in tumor cells, and vice versa. We found significant gene expression changes in MHC activation and downstream pathways in immune cells located nearest to tumor cells; in tumor cells nearest to immune cells, we identified increased expression of genes related to immune response mediation and inflammation. Furthermore, we compared the annotated immune cell populations across the various cancer types to observe differences in gene expression. Here, we used publicly available single-cell RNA-sequencing data to impute gene expression for these immune cell populations. This analysis demonstrated the transcriptional variation possible in identical immune cell types that are acting in different tissue contexts. Notably, we were able to map and catalogue different patterns of gene expression relating to inflammation, immune signaling, and immune cell exhaustion. These findings demonstrate how the MERSCOPE platform can provide deep insights into the complex heterogeneity observed between different tumor types and tissues. Citation Format: Ben Patterson, g-Yi Chen, Nicolas Fernandez, Leiam Colbert, Jiang He. Interrogating immuno-oncological interactions in the tumor microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5148.