The Center for Tumor-Immune Systems Biology is organized around three central scientific projects that examine tumor-immune ecosystems in immunologically distinct microenvironments where current immune checkpoint-based (ICB) immunotherapies are ineffective and explore how to engineer improved immune responses through immunogenic cancer cell death in contexts where ICB has had clinical efficacy. A Shared Resource Core will establish computational methods and technologies for spatial expression analyses in support of all three research projects.
Systems analysis of tumor-stroma interactions in brain metastasis
We will apply systems-level computational approaches to mouse models and clinical samples to unravel the different strategies metastatic cancer cells employ in coopting the brain microenvironment.
Immune regulatory circuits in primary colon cancer and lymph node and liver metastases
We will employ sophisticated genetic tools to perturb cellular circuits of regulatory and conventional T cells in colon cancer together with novel gene regulatory models trained on single-cell multiome data, coupled to spatial expression analyses in order to dissect immune regulation in this system. We will also use patient-derived colorectal organoids to model the consequences of immune-derived factors on cancer cells.
Engineering immunogenic cell death in melanoma and renal cell carcinoma
We will carry out a side-by-side comparison of multiple forms of immunogenic cell death as well as immunologically silent apoptosis engineered in models of melanoma and renal cell carcinoma, the two ICB-responsive cancers. Our goal is to identify the most therapeutically efficient form of immunogenic cell death that not only kills cancer cells but also enables the immune system to enhance ICB response and to generate durable anti-tumor immunity affording long-term disease-free survival.