Comprehensive profiling the immune-status of a broad range of in vivo syngeneic models to support IO development and to accurately predict clinical benefit of therapy

Abstract

Abstract Latterly with approval of PD-1, PD-L1 antibodies in clinical oncology, immunotherapy has gained recognition for changing the way of cancer treatment by joining chemotherapy, radiation and surgery. Murine syngeneic tumor models are critical to novel immuno-based therapy development. Therefore, understood the nature immune status and tumor microenvironment of in vivo tumor models is very important to assist exploring immunotherapy. However, the translational relevance of differences between the models is not fully understanding. Herein, we extensively characterize various murine syngeneic tumor models, which revealed striking differences in immune status and tumor microenvironment. These will contribute to appropriate preclinical model selection for target validation and drug development. In this study, nearly 51 tumor cell lines over a broad range of tumor types as well as corresponding in vivo syngeneic models were intensively studied on their immune status under two conditions that tumor volume were 100 mm3 and 500 to 600 mm3. The effort has been focusing on the immune status including T cell status and levels of immune-suppression via FACS analysis of the population of CD45+ TILs, CD4+ T cell, CD8+ T cell, Tregs, MDSCs, macrophage. Furthermore, the expressions of immune related genes were analyzed by RT-PCR. The profiling data illustrated the expression of these genes are different on different tumor models. We believe that this profiling data will help many scientists to properly select correct model to support R&D and better understand how immune therapeutically agent acts in the immune system.