Lymph node metastasis-induced stiffening impairs T cell egress in hepatocellular carcinoma
This study investigates whether lymph node metastasis in hepatocellular carcinoma elevates lymph node stiffness, thereby functionally restraining T cell egress from metastatic lymph nodes, and explores the underlying molecular mechanisms. We isolate T cells from lymph nodes of hepatocellular carcinoma patients with or without lymph node metastasis, and treat them with the pharmacological softening strategies, the TGFB type I receptor inhibitor A83-01, the LOX inhibitor BAPN, and collagenase, to modulate the mechanical microenvironment. Transcriptomic profiling is performed to compare differential gene expression across groups, with a focus on pathways governing T cell migration, mechanotransduction, and S1PR1 signaling. This study aims to establish a causal link between lymph node stiffening and T cell retention in lymph node metastasis within hepatocellular carcinoma.