Targeting PI3Kδ suppresses pancreatic cancer by dual disruption of fibrosis and immune evasion.
1/5 보강
Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stromal fibrosis that promotes immune exclusion and treatment resistance, yet the upstream drivers of this pro-fibrotic cascade remain
APA
Garczyk M, Outeiro-Pinho G, et al. (2026). Targeting PI3Kδ suppresses pancreatic cancer by dual disruption of fibrosis and immune evasion.. Cell reports, 45(4), 117188. https://doi.org/10.1016/j.celrep.2026.117188
MLA
Garczyk M, et al.. "Targeting PI3Kδ suppresses pancreatic cancer by dual disruption of fibrosis and immune evasion.." Cell reports, vol. 45, no. 4, 2026, pp. 117188.
PMID
41915470 ↗
Abstract 한글 요약
Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stromal fibrosis that promotes immune exclusion and treatment resistance, yet the upstream drivers of this pro-fibrotic cascade remain poorly defined. Here, we identify phosphoinositide 3-kinase δ (PI3Kδ) as a previously unrecognized driver of fibrosis in PDAC. Pharmacological inhibition of PI3Kδ reduces collagen deposition while enhancing the infiltration of activated CD8 T cells, thereby reprogramming the tumor microenvironment toward an antitumor state. Mechanistically, we reveal that PI3Kδ regulates the biosynthesis of lysophosphatidic acid (LPA), a key lipid mediator of stromal remodeling, by controlling phosphatidylcholine-derived precursors in both cancer cells and stromal fibroblasts. By regulating both LPA-driven stromal remodeling and immune suppression, PI3Kδ emerges as a central regulator of the PDAC tumor microenvironment. Co-inhibition of autotaxin, an enzyme contributing to LPA production, and PI3Kδ further amplifies stromal disruption and improves chemo-immunotherapy efficacy in preclinical PDAC models. These findings position PI3Kδ as a central therapeutic target in PDAC, offering a dual-action strategy to simultaneously dismantle stromal fibrosis and immune suppression.
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