Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths. Most cases of HCC (approximately 90%) occur in cirrhotic livers and progress in an inflammatory context. The incidence of HCC is increasing in industrialized countries and the prognosis of patients with advanced HCC is still very poor, despite significant progress in the diagnosis and curative strategies of HCC. Cancer stem cells (CSCs) have recently sparked the interest of scientists because of their involvement in initiation and tumor growth processes. However, the mechanisms by which expansion of CSCs is initiated are still unclear.
The liver is considered to be an "immune" organ, as it contains a wide variety of immune cells. After severe and/or chronic liver injury, the liver progenitor cell (LPC) compartment is activated by a sustained inflammatory response. LPCs participate in the regenerative process and are also present in HCC. Various types of immune cells are frequently observed in the microenvironment of HCC. Among the large spectrum of released cytokines, recent studies have identified IL-17, produced by a sub-population of T lymphocytes called Th17 cells. An increase in the number of IL-17-producing cells has been observed in a variety of chronic liver diseases, alcoholic liver disease, chronic viral hepatitis, and cirrhosis. The presence of IL-17 is associated with a poor prognosis for HCC patients. We recently showed that IL-17 has a pro-inflammatory and pro-fibrogenic role in the liver.
Our goals are:
Interleukins-17 and 27 promote liver regeneration by sequentially inducing progenitor cell expansion and differentiation
Hepatology Communications 2018
Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship With clinical and pathological features
Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver
STAT proteins - key regulators of anti-viral responses, inflammation, and tumorigenesis in the liver
J Hepatol. 2012
Hepatoprotective versus oncogenic functions of STAT3 in liver tumorigenesis
Am J Pathol. 2011
Th17 cells and their associated cytokines in liver diseases
Cell Mol Immunol. 2010
Myeloid STAT3 inhibits T cell-mediated hepatitis by regulating T helper 1 cytokine and interleukin-17 production