LRRC15+ myofibroblasts dictate the stromal setpoint to suppress tumour immunity

Abstract Recent single-cell studies of cancer in both mice and humans have identified the emergence of a myofibroblast population specifically marked by the highly restricted leucine-rich-repeat-containing protein 15 (LRRC15) 1–3 . However, the molecular signals that underlie the development of LRRC15 + cancer-associated fibroblasts (CAFs) and their direct impact on anti-tumour immunity are uncharacterized. Here in mouse models of pancreatic cancer, we provide in vivo genetic evidence that TGFβ receptor type 2 signalling in healthy dermatopontin + universal fibroblasts is essential for the development of cancer-associated LRRC15 + myofibroblasts. This axis also predominantly drives fibroblast lineage diversity…

• A
  Amgen
• BS
  Bristol-Myers Squibb
• P
  Pfizer
• G
  Genentech
• UO
  University of California, San Francisco