Liver Inflammation Impairs Immunotherapy by Hindered T Cell Activity
Research reveals that liver inflammation caused by cancer suppresses the immune system’s ability to fight tumors. Cancer-induced inflammation triggers liver cells to release serum amyloid A (SAA) proteins, which hinder T cell infiltration and attack on tumors. This finding highlights the role of liver inflammation as an immune checkpoint and identifies potential therapeutic targets to enhance immunotherapy effectiveness.
Previous studies by the team had established the role of liver inflammation in promoting tumor metastasis and reducing immunotherapy responses. This latest investigation delved deeper into the mechanisms underlying liver inflammation’s immune-suppressing effects.
Using mouse models of pancreatic cancer, researchers observed an inverse correlation between liver inflammation and T cell infiltration into tumors. They identified the IL-6/JAK/STAT3 pathway as a key signaling pathway involved in this process. Activation of STAT3 in liver cells reduced the production of dendritic cells, which are essential for T cell responses.
The research team demonstrated that STAT3 activation in liver cells induces SAA protein production, which in turn suppresses dendritic cell and T cell activity. Deleting SAA proteins restored immune function, increased tumor infiltration by T cells, and improved survival in mice with pancreatic tumors.
Analysis of human pancreatic tumor samples revealed a correlation between low SAA levels at surgery and longer patient survival. This translational finding supports the clinical relevance of the mouse model findings.
The study has important implications for cancer immunotherapy strategies. By targeting liver inflammation through STAT3 or SAA inhibition, it may be possible to enhance immunotherapy efficacy and improve cancer patient outcomes. Preclinical and clinical studies are underway to evaluate the potential of these agents as add-on therapies to immunotherapy.
