This paper details how macropinocytosis—a cellular process for scavenging extracellular fluids—is crucial for maintaining the identity of myofibroblasts (myCAFs), a subtype of cancer-associated fibroblasts (CAFs), in pancreatic cancer, specifically under glutamine stress. The authors, Zhang et al., demonstrate that inhibiting macropinocytosis in CAFs forces a shift from myCAFs to the inflammatory iCAF subtype via a MEK-ERK-dependent intermediate state. This CAF plasticity fundamentally alters the tumor microenvironment by reducing collagen deposition and increasing vascular expansion, which enhances the infiltration of T cells and improves the efficacy of both immunotherapy and chemotherapy in models of pancreatic ductal adenocarcinoma (PDAC). Consequently, the research positions macropinocytosis inhibition as a viable strategy for combination treatment to improve outcomes in PDAC.

References:

• Zhang Y, Ling L, Murad R, et al. Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer[J]. Cancer Cell, 2025, 43(9): 1677-1696. e15.