Abstract 5871: Comparative analysis of single-cell immune cell transcriptional profiles in humans, mice, and dogs: insights from normal and tumor states

Abstract The immune system plays a critical role in defending against pathogens and surveilling tumors. Understanding immune cell behavior in both health and disease is essential for advancing therapeutic strategies, particularly in oncology. However, there remains a gap in knowledge regarding how immune cell profiles differ across species and how these differences might impact cancer immunology. In this study, we conduct a comparative analysis of single-cell transcriptional profiles of immune cells from three mammalian species—humans, mice, and dogs—under both normal and tumor-bearing conditions. Using high-throughput single-cell RNA sequencing (scRNA-seq), we aim to identify both conserved and species-specific transcriptional signatures that define immune cell function in health and cancer, with the ultimate goal of enhancing translational research and therapeutic development. To generate a comprehensive dataset, we analyzed immune cell samples from both normal and tumor tissues across humans, mice, and dogs. These species were selected for their distinct immunological and clinical features: humans as the primary model for clinical oncology, mice as the standard laboratory model for cancer research, and dogs as a naturally occurring cancer model with genetic and environmental similarities to humans. Immune cells from canine samples were isolated and analyzed using scRNA-seq. Publicly available human, mouse and canine datasets were also incorporated into the analysis. Analyses of these datasets enabled high-resolution characterization of the immune landscape in each species. We developed a pipeline to systematically identify both commonalities and species-specific differences in immune cell transcriptional profiles. In tumor free samples, immune cell profiles were broadly similar across species, with T cells, B cells, macrophages, and dendritic cells as the dominant populations. However, we also observed notable species-specific variations in the transcriptional features of immune cells in normal and tumor tissue. This study provides a comprehensive cross-species analysis of immune cell transcriptional profiles in both normal and tumor states. Our findings highlight the importance of considering species-specific differences when translating preclinical results to human cancer research, emphasizing the value of utilizing multiple animal models, including canines, to enhance our understanding of cancer immunology. These insights are critical for the design of immunotherapies and the optimization of preclinical cancer models. Citation Format: Aaron L. Sarver, Caitlyn M. Callaghan, Marissa Macchietto, Lauren Burt, Meagan Wojtysiak, Courtney H. Labé, Taylor DePauw, Ashley Schulte, Kelly M. Makielski, Julia E. Medland, Jaime F. Modiano. Comparative analysis of single-cell immune cell transcriptional profiles in humans, mice, and dogs: insights from normal and tumor states [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5871.