Published November 5, 2021
| Version v1
Journal article
Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients
Creators
- Palle, Juliette
- Hirsch, Laure
- Lapeyre-Prost, Alexandra
- Malka, David
- Bourhis, Morgane
- Pernot, Simon
- Marcheteau, Elie
- Voron, Thibault
- Castan, Florence
- Lacotte, Ariane
- Benhamouda, Nadine
- Tanchot, Corinne
- François, Eric
- Ghiringhelli, François
- de la Fouchardière, Christelle
- Zaanan, Aziz
- Tartour, Eric
- Taieb, Julien
- Terme, Magali
Contributors
Others:
- Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)) ; Hôpital Européen Georges Pompidou [APHP] (HEGP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay
- Biostatistics Unit, CTD INCa, ICM-Montpellier Cancer Institute
- Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UCA)
- Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL) ; UNICANCER
- Medical Oncology Department, Centre Léon Bérard, Lyon
- Department of Gastrointestinal Oncology, AP-HP, HEGP, Université de Paris
Description
Elucidating mechanisms involved in tumor-induced immunosuppression is of great interest since it could help to improve cancer immunotherapy efficacy. Here we show that Hepatocyte Growth Factor (HGF), a pro-tumoral and proangiogenic factor, and its receptor c-Met are involved in regulatory T cells (Treg) accumulation in the peripheral blood of gastric cancer (GC) patients. We observed that c-Met is expressed on circulating monocytes from GC patients. The elevated expression on monocytes is associated with clinical parameters linked to an aggressive disease phenotype and correlates with a worse prognosis. Monocyte-derived dendritic cells from GC patients differentiated in the presence of HGF adopt a regulatory phenotype with a lower expression of co-stimulatory molecules, impaired maturation capacities, and an increased ability to produce interleukin-10 and to induce Treg differentiation in vitro. In the MEGA-ACCORD20-PRODIGE17 trial, GC patients received an anti-HGF antibody treatment (rilotumumab), which had been described to have an antiangiogenic activity by decreasing proliferation of endothelial cells and tube formation. Rilotumumab decreased circulating Treg in GC patients. Thus, we identified that HGF indirectly triggers Treg accumulation via c-Met-expressing monocytes in the peripheral blood of GC patients. Our study provides arguments for potential alternative use of HGF/c-Met targeted therapies based on their immunomodulatory properties which could lead to the development of new therapeutic associations in cancer patients, for example with immune checkpoint inhibitors.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal-univ-paris.archives-ouvertes.fr/hal-03788546
- URN
- urn:oai:HAL:hal-03788546v1
Origin repository
- Origin repository
- UNICA