The immune composition of tumor microenvironments is highly heterogenous and has decisive impacts on disease progression and therapy responses. Understanding how tumors shape their immune microenvironment, and how immune cells affect cancer cells, is essential to develop cancer treatments adapted to each patient.
Our lab addresses this question following a three-step process:
1) Profiling: we use state-of-the-art profiling technologies, including scRNAseq and spatial transcriptomics, to reveal the heterogeneity of human cancers and identify landmark immune microenvironments.
2) Using our advanced humanized mouse models, we develop and validate models of human cancer representative of each landmark microenvironment
3) We use diverse experimental perturbation (including specific cell depletion or gene knockout) in humanized mice to test hypothesis on the mechanistic basis of cancer-immune cell interactions in vivo, or to test novel candidate therapies.
We are using this approach to address several questions in immuno-oncology, including:
- What are the mechanisms determining whether T cells can infiltrate or not the tumor microenvironment (hot vs cold tumors)?
- How are heterogenous macrophage landscapes established in tumors, and how do macrophages impact disease progression?