Celebrating the 10th Anniversary
A decade of discoveries in Cancer Discovery. For the community. By the Community.
Research
Single-cell Insights into Pancreatic Cancer
The advent of single-cell sequencing approaches over the past several years has allowed new insights that have advanced our understanding of the complexity and heterogeneity of many cancer types, but particularly pancreatic ductal adenocarcinoma (PDAC), which is distinguished by a dense stroma containing many different nonmalignant cell types that support tumor proliferation, survival, and invasion. Cancer-associated fibroblasts (CAF) are particularly abundant in PDAC stroma, with evidence suggesting a heterogeneous population of cells with distinct functions. In 2019, Elyada, Robson, Tuveson, and colleagues performed single-cell RNA sequencing on human PDAC tissue and normal pancreas and tumor tissue from genetically engineered PDAC mouse models, providing the first insights into CAF heterogeneity at single-cell resolution. They catalogued various nonmalignant stromal cell types in both human and mouse PDAC, including ductal epithelial cells, myeloid and lymphoid cell types associated with an immune- suppressive microenvironment, and several different subsets of CAFs, including a previously uncharacterized CAF subtype that expressed MHC class II family genes and could present antigens to T cells ex vivo. Dubbed antigen-presenting CAFs, or apCAFs, these cells differed from canonical antigen-presenting cells in that they did not express costimulatory molecules necessary to induce T- cell proliferation, suggesting that they might act as decoys to promote immune suppression in the PDAC microenvironment. Uncovering the stromal complexity of PDAC has galvanized the field to interrogate the roles of these different cell types in the hopes of developing improved therapeutic strategies.
