CCBIO webinar: Huocong Huang
Heterogeneity of cancer-associated fibroblasts in pancreatic cancer
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
Pancreatic cancer is a lethal disease characterized by extensive desmoplasia caused by the rapid expansion of cancer-associated fibroblasts (CAFs), resulting in the formation of dense stroma. CAFs stimulate cancer progression by secreting a variety of factors that support cancer cells and facilitate immunosuppression. In addition, they also secrete extracellular matrix that provides survival and invasion cues to cancer cells and impairs drug delivery. Recently, several populations of CAFs with distinct functions have been characterized in pancreatic cancer by our group and others using single cell RNA sequencing techniques. One population is characterized as myofibroblastic CAFs, another population is characterized as inflammatory CAFs, the third population was identified as antigen-presenting CAFs (apCAFs), which express MHC II molecules and can effectively present antigen to T cells. However, the origin and functions of apCAFs remain unknown. By tracing the apCAFs in a cancer progression setting, we found that they originate from a cell type called mesothelial cells in normal pancreas. Mesothelial cells form a continuous layer of epithelial cells known as mesothelium. The mesothelium is traditionally thought to be a membrane providing a non-adhesive surface covering organs and tissues. However, until the description of apCAF population, mesothelial cells have been neglected as a potential functional constituent of the tumor microenvironment. Our data suggest that during cancer progression, mesothelial cells gain fibroblast features, become a major CAF population and are involved in the direct regulation of T cells in the tumor microenvironment.
Chairperson: James B. Lorens, CCBIO