Who we are
The Center for Cancer Evolution (CCE) was founded in 2016 by Drs. Michor, Pellman, and Polyak at the Dana-Farber Cancer Institute.
The CCE focuses on understanding cancer evolution through a multi-disciplinary approach. Our goal is to understand the mechanisms behind tumor evolution, metastasis formation, emergence of drug resistance to ultimately provide more specialized and effective patient care in a variety of different cancer types.
Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments. Nature Cell Biology, 2019
Most human tumours are heterogeneous, composed of cellular clones with different properties present at variable frequencies. Highly heterogeneous tumours have poor clinical outcomes, yet the underlying mechanism remains poorly understood. Here, we show that minor subclones of breast cancer cells expressing IL11 and FIGF (VEGFD) cooperate to promote metastatic progression and generate polyclonal metastases composed of driver and neutral subclones. Expression profiling of the epithelial and stromal compartments of monoclonal and polyclonal primary and metastatic lesions revealed that this cooperation is indirect, mediated through the local and systemic microenvironments. We identified neutrophils as a leukocyte population stimulated by the IL11-expressing minor subclone and showed that the depletion of neutrophils prevents metastatic outgrowth. Single-cell RNA-seq of CD45+ cell populations from primary tumours, blood and lungs demonstrated that IL11 acts on bonemarrow-derived mesenchymal stromal cells, which induce pro-tumorigenic and pro-metastatic neutrophils. Our results indicate key roles for non-cell-autonomous drivers and minor subclones in metastasis.