Senescent cancer-associated fibroblasts drive early-stage lymph node metastasis in pancreatic cancer through lactate-mediated metabolic-epigenetic rewiring - PubMed
3 hours ago
- #Pancreatic Cancer
- #Senescent Fibroblasts
- #Lymph Node Metastasis
- Senescent cancer-associated fibroblasts (senCAFs) drive lymph node metastasis (LNM) in early-stage pancreatic cancer (PDAC) by promoting lymphatic remodeling.
- senCAFs increase glucose metabolism and lactate production, activating lactylation-mediated serine metabolism to protect lymphatic endothelial cells from oxidative stress.
- CCR4+ Tregs accumulate around lymphatic vessels in draining lymph nodes, creating an immunosuppressive peri-lymphatic niche.
- High-throughput drug screening identified chidamide as a selective senolytic agent that clears senCAFs, attenuating tumor progression and improving chemo-immunotherapy efficacy.
- A clinical trial combining chidamide with nab-paclitaxel/gemcitabine and anti-PD-1/CTLA-4 shows promising preliminary results in metastatic PDAC patients.