VHC - Virus Hépatologie Cancer | HENRI MONDOR

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   Fouad LAFDIL


Impact of the immune microenvironment in hepatocellular carcinoma initiation and
progression : innovative therapeutic strategies targeting the immune response


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:

  • To determine whether Th17 lymphocytes and IL-17 are involved in liver tumorigenesis by promoting the transformation of resident LPCs into CSCs. 
  • To decipher the mechanisms by which HCC escapes the anti-tumoral immune response.
  • To unravel the mechanisms involved in HCC resistance to current anticancer therapies.

Team Members

  • Yeni Ait-Ahmed, PhD
  • Arthur Brouillet, PhD, MCU
  • Camilia Machou, PhD
  • Aurélie Rodrigues, PhD
  • Benoît Rousseau, MD, PhD


  • Julien Calderaro, INSERM U955 , Pathology Anatomy and cytology Department -Henri Mondor Hospital
  • Bruno Clément, INSERM U1241, INRA U13411 - Rennes Hospital
  • Bin Gao, Laboratory of Liver Diseases - National Institute on Alcohol Abuse and Alcoholism - National Institutes of Health
  • Alain Luciani, INSERM U955 , Medical imagery Department, Henri Mondor Hospital
  • Christophe Rodriguez, Platform for the characterization of microbial genomes by hugh throughput sequencing