Celebrating the 10th Anniversary
A decade of discoveries in Cancer Discovery. For the community. By the Community.
Their impactful studies. In their words.
This was the first description of a single cell analysis of human and mouse pancreatic cancer, and it revealed tremendous complexity in both neoplastic cells and the tumor microenvironment.
Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts.
Q: What unanswered questions in the field were these studies addressing?
A: (David A. Tuveson) This collaboration between the Tuveson lab at CSHL and the Robson lab at JAX represented a culmination of a long-standing collaboration between our cancer centers, and has led to a new NCI co-PI grant to support further work. This was the first description of a single cell analysis of human and mouse pancreatic cancer, and it revealed tremendous complexity in both neoplastic cells and the tumor microenvironment. The cross-species comparison of human and mouse PDAC confirmed the fibroblast subsets we previously published and identified a new subtype that expressed MHC Class 2, and therefore possessed potential immunomodulatory functions. Many groups have confirmed our initial report and have extended it to other questions in the PDAC field.
Q: What surprised or excited you most about the findings?
A: (Ela Elyada) For me, this was the first study to deeply interrogate the PDAC microenvironment, and the first zoom-in on cancer-associated fibroblasts (CAFs) at the single cell level. As Dave mentioned, the most exciting finding was the new fibroblast subset – antigen-presenting CAFs (apCAFs) – which was then validated by other groups and was found to exist in other cancer types as well. The fact that these cells can actually interact with CD4+ T cells opens new questions and possibilities for cancer immunology.
Q: What have been the papers’ greatest impacts in the years to follow?
A: (Paul Robson) I fully agree with the points Dave and Ela have made. In addition, the data generated in this study, specifically of the human primary tumors, continues to inform the development of advanced models of PDAC (e.g., PDX and organoids.)