Unraveling the Tumor-Immune Microenvironment by Immunogenomic Analysis
We are combining experimental and computational approaches to understand interactions between immune cells and tumor cells and how they shape the variability observed in tumor-infiltrating lymphocytes (TILs) across cancers of different tissue types. The research questions we will address include: how pervasive is intra-patient TIL variability in tumors from patients with metastatic disease, what are the mechanisms behind tumor-immune microenvironmental heterogeneity, and how does standard-of-care chemotherapy perturb the immune microenvironment? By leveraging our clinical, immunological, and computational expertise, we will analyze immune cell populations in our genomically-profiled tumor tissue bank, hereby enabling us to develop, benchmark, and apply informatic methods for analysis of TILs based on bulk tumor mRNA data. By iterating between method development and benchmarking on TIL-quantified tumor samples, we can not only develop new informatics tools, but also use our models to predict new characteristics of the tumor microenvironment and understand how the tumor-immune interactions change upon therapeutic treatment.
Additional links to papers relating to this project:
Jimenez-Sanchez A, O Cast & ML Miller
Comprehensive Benchmarking and Integration of Tumour Microenvironment Cell Estimation Methods
Cancer Research, 79 (24), 6238-6246 (2019)
Jimenez-Sanchez A, P Cybulska, K Lavigne, S Koplev, O Cast, D-L Couturier, P Selenica, Y Bykov, G Macintyre, L Morrill, R Drews, M Gill, T Walther, I Nikolovski, Y Mazaheri, B Weigelt, DS Chi, J Park, T Hollmann, J Reis-Filho, R Shen, P Beltrao, F Markowetz, A Vargas, D Zamarin, J Brenton, A Snyder, E Sala, ML Miller
Unraveling Tumor-Immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy