UMR INSERM U1242-OSS SPECIAL SEMINAR - Centre De Lutte Contre Le Cancer Eugène Marquis

Targeting cancer-associated fibroblast to improve immunotherapy in liver cancer

Romain DESERT

Pharmacist and research scientist

Institute for Translational Medicine and Liver Disease (ITM)

Inserm U1110 - STRASBOURG

Abstract

Liver cancer is the one of the top leading causes of cancer-related death worldwide. While the clinical introduction of immunotherapy has improved response rates and overall survival, their clinical success remains still limited, underlying the need for novel therapeutic strategies. Liver cancer arise in a fibroinflammatory microenvironment involving extracellular matrix (ECM) deposition by cancer-associated fibroblasts. ECM remodeling has been shown to play a critical role in carcinogenesis and cancer progression and to be involved in immunotherapy response and resistance. In liver cancer, CAF activation leads to a cancer-specific ECM remodeling expressed in a subset of patients expressing a distinctive molecular and immune phenotype associated with the response to immunotherapy. Furthermore, analysis of fibroblasts atlases showed that this cancer-specific fibrosis is secreted by a small set of fibroblast subtypes. Thus, targeting fibroblast subtypes is a promising strategy to improve the therapeutic options for patients with liver cancer.