Presenter: Dr. Tao Wang (UT Southwestern Medical Center, Dallas, USA)
Topic: An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors
Time: 14:00PM, April. 9th (Monday)
Location: Conference Room 910-308
By leveraging tumorgraft (PDX) RNA-Seq data, we developed an empirical approach, DisHet, to dissect the tumor microenvironment (eTME). We found that 65% of previously defined immune signature genes are not abundantly expressed in Renal Cell Carcinoma (RCC), and identified 610 novel immune/stromal transcripts. Using eTME, genomics, pathology and medical record data involving >1,000 patients, we established an inflamed pan-RCC subtype (IS) enriched for Tregs, NK cells, Th1 cells, neutrophils, macrophages, B cells, and CD8+ T cells. IS is enriched for aggressive RCCs, including BAP1-deficient clear-cell and type 2 papillary tumors. The IS subtype correlated with systemic manifestations of inflammation such as thrombocytosis and anemia, which are enigmatic predictors of poor prognosis. Furthermore, IS was a strong predictor of poor survival. Our analyses suggest that tumor cells drive the stromal immune response. These data provide a missing link between tumor cells, the TME, and systemic factors.
Assistant Professor of the Quantitative Biomedical Research Center in the Department of Clinical Sciences at UT Southwestern Medical Center, Dr. Wang's research revolves around using state-of-the-art quantitative approaches to study the implications of tumor heterogeneity for tumorigenesis, metastasis, prognosis, and treatment response, primarily focused on kidney cancer (renal cell carcinoma, RCC). Dr. Wang is also affiliated with the Harold C. Simmons Comprehensive Cancer Center, along with the Center for the Genetics of Host Defense. He is also the Bioinformatics co-Leader of the Kidney Cancer Program of UT Southwestern and serves as the Data Analytics Core Co-Director within the UT Southwestern SPORE for kidney cancer research. Dr. Wang graduated from Peking University in China in 2011 and studied at UT Southwestern under the mentoring of Drs. Yang Xie and Guanghua Xiao. He became an Assistant Professor at UTSW after obtaining his Ph.D. in 2015. His research is mainly focused on profiling the immune cell infiltrates and stromal pathway activations in tumor stroma and understanding their interactions with the tumor cells and implication for therapeutic responsiveness. His research also focuses on how heterogeneous cancers can be better categorized according to their molecular abnormalities. Besides, he created the LinkageAnalyzer software for statistical mapping of phenotype-genotype in mouse forward genetic screening data. LinkageAnalyzer is being run daily for the Mutagenetix consortium led by Dr. Bruce Beutler, which is a large-scale screening project focused on identifying immune-response genes from ENU-mutated mice. So far, he has published several brilliant work in top journals, including in Nature Biotechnology, Lancet Oncology, Nature Communications, JCO Clinical Cancer informatics, PLOS Pathogens, Nucleic Acid Research.
Contact: Prof. Jian Chen