Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients.
Fiche publication
Date publication
novembre 2021
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François
Tous les auteurs :
Palle J, Hirsch L, Lapeyre-Prost A, Malka D, Bourhis M, Pernot S, Marcheteau E, Voron T, Castan F, Lacotte A, Benhamouda N, Tanchot C, François E, Ghiringhelli F, de la Fouchardière C, Zaanan A, Tartour E, Taieb J, Terme M
Lien Pubmed
Résumé
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 anti-angiogenic 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.
Mots clés
anti-HGF, c-Met, gastric cancer, hepatocyte growth factor, pro-angiogenic factor, regulatory T cells, targeted therapies
Référence
Cancers (Basel). 2021 Nov 5;13(21):