Lymph node metastasis remodels H3K4me3 landscapes and suppresses transcriptional activity of T cells in hepatocellular carcinoma
When liver cancer spreads to lymph nodes, it changes the immune environment inside those nodes. How this spread affects T cell gene regulation is still unclear. We collected lymph nodes from liver cancer patients. Some patients had lymph node metastasis and some did not. We purified T cells from these lymph nodes and used H3K4me3 ChIP to map active gene promoters across the genome. We found that T cells in metastatic lymph nodes have much lower H3K4me3 levels at many gene promoters. Genes controlling T cell movement, immune function, and cell survival are hit the hardest. These results show that lymph node metastasis rewires T cell epigenetic programs and weakens their gene activity. This may explain why T cells fail to fight cancer well in patients with metastasis.