Cancer is increasingly recognized as a multifactorial disease, resulting from a dysregulated communication between different cell types of the tumor microenvironment, including cancer cells, innate and adaptive immune cells, as well as heterogeneous populations of stromal cells, altogether modulated by the host metabolism and the microbiota. Our previous investigations highlighted a critical role for ADAM9 and ADAM12 in prostate tumor progression, notably by altering the tumor-stromal crosstalk through shedding of growth factors essential in tumor proliferation and differentiation (such as EGF and FGFR2iiib).
We have recently shown that ADAM12+ mesenchymal cells play a key role in inducing an immunosuppressive tumor microenvironment by promoting pathological angiogenesis and hypoxia, in coordination with tumor macrophages.
CD3+ T cells are retained on the tumor margin, a transition zone containing several types of mesenchymal cells and immune cells. On the right, GFP identifies ADAM12+ perivascular mesenchymal cells (Di Carlo et al., Nature Immunology 2023)
Using different experimental approaches, including transcriptomic analysis at the single cell resolution, epigenetics, proteomics and pharmacological approaches, we are further exploring stromal heterogeneity and function in tumor immunity/progression and therapeutic resistance to anti-cancer treatments. We are investigating different tumor microenvironment, including breast cancer, pancreatic cancer and melanoma to assess stromal organ specificities.