A pre-clinical mouse model to recapitulate human colorectal cancer immune profiling and tumor microenvironment 4113

Abstract Description Tumor micro-environment plays a significant challenge in modeling colorectal cancer (CRC) for pre-clinical and therapeutic studies. The widely used orthotopic cecal wall procedure does not replicate the clinical location of human CRC tumors, a prerequisite for orthotopic animal models. In this study, we develop a non-surgical procedure to generate an orthotopic CRC mouse model, with tumors localized to the distal colon, that mimic the natural tumor microenvironment. Using a specialized catheter, the mouse colon was proximally blocked and aberrated followed by incubation with tumor cells to ensure proper localization for tumor formation. Tumor progression at various stages was verified through hematoxylin and eosin staining. We compared the tumor immune profiling with human scRNA seq data in both MSI and MSS models. Interestingly, the CD8+ and CD4+ T cell infiltration in our mouse model was comparable to human tumors. Data also showed a similar trend in Treg cell infiltration in MSI and MSS mouse model as in human CRC. Further, comparing the MDSCs population, we found similar infiltration patterns with increasing infiltration in MSI model compared to MSS mouse model. Comparative analysis revealed increased fibroblast infiltration (alpha-SMA) in MSS mouse model compared to MSI model resembling human CRC dataset. Collectively, these analyses showed a crucial overlap of our novel mouse model with human immune cell infiltration providing a better clinically relevant model for CRC. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)