Characterization of anti-tumor networks in tumor-associated macrophages 2377

Abstract Description Current cancer therapies often fail due to a highly immunosuppressive tumor microenvironment (TME), which impedes immune cells from effectively targeting and eliminating cancer cells. Tumor-associated macrophages (TAMs) have been shown to compose up to 50% of a tumor’s mass and have been shown to exist on a polarization spectrum from anti-tumoral to pro-tumoral depending on the direct and indirect effects they have on tumors. The objective of this project is to establish pathways that control TAM tumor phenotypes. To study which TAM pathways are most amenable to manipulation to drive anti-tumor efficacy, we utilized a multi-omics approach which combines single cell RNA sequencing (scRNA-seq), spatial transcriptomics, and imaging mass spectrometry. We integrated publicly available datasets with datasets we developed from our mouse model of orthotopic pancreatic ductal adenocarcinoma (PDAC). These techniques allowed the identification of alterations in TAM metabolic networks associated with markers known to be a part of macrophage reprogramming such as Arg1, Spp1, and C1q, but the mechanism of how this shift can drive the phenotype is still to be elucidated. Future work will focus on identifying key genes involved in TAM metabolic reprogramming and assessing whether targeting these genes can modulate tumor growth by altering TAM activity. Ultimately, this research seeks to define actionable pathways that can be manipulated to enhance TAM-mediated anti-tumor responses. Funding Sources NIH K00CA274682-03 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)