Comprehensive Profiling of The Immune Status of A Broad Range of in Vivo Syngeneic Models to Support IO Development and to Accurately Predict Clinical Benefit of Therapy

Author(s): Wentao Li, Jinghui Xiu, Liang Yao, Qiuliang Li, Guannan Li, Xiaodong Li, Lu Zhang, Chunhong Ning, Wei Yun, Shizong Hu, Jingqi Huang

Recently, with the approval of anti-PD-1 and anti-PD-L1 antibodies in clinical oncology, immunotherapy has changed the approach to cancer treatment and joins chemotherapy, radiation, and surgery as treatment options. Murine syngeneic tumor models are critical to the development of novel immuno-based therapy. Understanding the nature of the immune status and the tumor microenvironment of in vivo tumor models is essential to explore immunotherapy. However, the translational relevance of differences between the models is not fully understood. Therefore, we extensively characterized various murine syngeneic tumor models, which revealed striking differences in immune status and in tumor microenvironment. These findings will contribute to the appropriate selection of preclinical models for target validation and drug development. In this study, 49 tumor models over a broad range of tumor cell types, as well as corresponding in vivo syngeneic models, were intensively studied for their immune status under two conditions: tumor volume of 100 mm3 or tumor volume between 500 to 600 mm3. Immune status was determined by measuring T cell status and levels of immune-suppression via FACS analysis of the population of tumor-infiltrating leukocytes (TILs), CD45+ T cells, CD4+ T cells, CD8+ T cells, T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSCs), and macrophages. Furthermore, the expression of immune-related genes was analyzed by RT-PCR. Profiling data revealed the expression of these genes was different for different tumor models. We believe that this profiling data will help many scientists to properly select the correct model to support research and development, and better understand how immunotherapy agents act on the immune system.