Delineating the Cellular Taxonomy of the Cancer Microenvironment
We propose that a tumor should be considered as a communicating organ in its own right comprising multiple cell types that collectively evolve into a clinically manifested and deadly disease. We believe that decisive treatment benefit can only be achieved by targeting multiple but distinct cell types that collectively sustain malignant growth.
Our overarching aim is to functionally define the cellular elements of a tumor. Studies of the tumor microenvironment continuously alert us to new cell types that perform important accessory functions during malignant conversion. Indeed, subsets of various cell types within tumors can be distinguished by differential marker expression and may hold functional significance. Cancer-associated fibroblasts (CAFs) are the most prevalent constituent cell type in the tumor microenvironment in many cancers, including breast, pancreas and hepatic carcinomas. While CAFs have been documented to endorse many, if not all, hallmarks of cancer, recent studies also ascribe tumor-restricting functions to mesenchymal cells in certain circumstances, suggestive of a functional heterogeneity within the broadly defined CAF population. Here, the student will unravel the complexity of CAFs by ascribing functional roles to observed subgroups of CAFs through the use of state-of-the-art analyses at single cell resolution. Taken together, the ultimate goal of the work is to present an improved cellular, molecular and functional taxonomy of CAFs, opening up the possibility for development of novel targeted drugs and biomarkers of clinical significance with improved precision.