Tumor site-specific immune profiling and infiltration influence tumor microenvironment in colorectal cancer mouse models 4112

Abstract Description Immunotherapy is transforming CRC treatment, but the traditional cecal wall model lacks clinical relevance by failing to replicate human tumor location and microenvironment. To bridge this gap, we developed a novel site-specific non-surgical orthotopic model that closely mimics the clinical settings. Comparative tumor growth and immunophenotyping of these models were performed in BALB/c and C57BL/6 mice, representing microsatellite stable (MSS) and microsatellite instability (MSI) models, respectively, to reveal an immune-responsive CRC model. Flow cytometry was employed to analyze the tumor’s immune cell composition and functional state. We observed a significant decrease in CD4+ T cell infiltration in MSS tumors generated using the non-surgical procedure, accompanied by an increase in Tregs, indicative of a more immunosuppressive tumor microenvironment. Reduced PD-1 expression on CD8+ T cells in tumors from BALB/c mice further supports this finding, highlighting the potential for immune checkpoint blockade therapy in this model. Additionally, elevated KLRG1 expression on CD4+ T cells suggests impaired T cell function and reduced IL-2 production. Conversely, a less immunosuppressive phenotype in tumors generated using the non-surgical procedure compared to the cecal wall model was observed in the MSI model. These findings suggest that the non-surgical procedure is an immunologically predictive CRC model, facilitating the preclinical evaluation of potential therapies. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)