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Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients.
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.
Afiliación
  • Palle J; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Hirsch L; Department of GI Oncology, AP-HP, Hôpital Européen Georges-Pompidou, Université de Paris, 75015 Paris, France.
  • Lapeyre-Prost A; Equipe Labellisée Ligue Contre le Cancer, 31037 Toulouse, France.
  • Malka D; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Bourhis M; Department of Medical Oncology, Hopital Cochin, Assistance Publique-Hôpitaux de Paris, Université de Paris, 75015 Paris, France.
  • Pernot S; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Marcheteau E; Department of GI Oncology, AP-HP, Hôpital Européen Georges-Pompidou, Université de Paris, 75015 Paris, France.
  • Voron T; Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France.
  • Castan F; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Lacotte A; Equipe Labellisée Ligue Contre le Cancer, 31037 Toulouse, France.
  • Benhamouda N; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Tanchot C; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • François E; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Ghiringhelli F; Biostatistics Unit, CTD INCa, ICM-Montpellier Cancer Institute, 34090 Montpellier, France.
  • de la Fouchardière C; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Zaanan A; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Tartour E; Department of Immunology, AP-HP, Hopital Européen Georges Pompidou, 75015 Paris, France.
  • Taieb J; Université de Paris, Inserm, PARCC, 75015 Paris, France.
  • Terme M; Equipe Labellisée Ligue Contre le Cancer, 31037 Toulouse, France.
Cancers (Basel) ; 13(21)2021 Nov 05.
Article en En | MEDLINE | ID: mdl-34771724
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza