Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients

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 (T...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Juliette Palle, Laure Hirsch, Alexandra Lapeyre-Prost, David Malka, Morgane Bourhis, Simon Pernot, Elie Marcheteau, Thibault Voron, Florence Castan, Ariane Lacotte, Nadine Benhamouda, Corinne Tanchot, Eric François, François Ghiringhelli, Christelle de la Fouchardière, Aziz Zaanan, Eric Tartour, Julien Taieb, Magali Terme
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hepatocyte growth factor c-Met pro-angiogenic factor regulatory T cells gastric cancer targeted therapies Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c25ad10896804800b263589545bd4b25
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c25ad10896804800b263589545bd4b25
record_format	dspace
spelling	oai:doaj.org-article:c25ad10896804800b263589545bd4b252021-11-11T15:35:11ZTargeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients10.3390/cancers132155622072-6694https://doaj.org/article/c25ad10896804800b263589545bd4b252021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5562https://doaj.org/toc/2072-6694Elucidating 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.Juliette PalleLaure HirschAlexandra Lapeyre-ProstDavid MalkaMorgane BourhisSimon PernotElie MarcheteauThibault VoronFlorence CastanAriane LacotteNadine BenhamoudaCorinne TanchotEric FrançoisFrançois GhiringhelliChristelle de la FouchardièreAziz ZaananEric TartourJulien TaiebMagali TermeMDPI AGarticlehepatocyte growth factorc-Metpro-angiogenic factorregulatory T cellsgastric cancertargeted therapiesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5562, p 5562 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatocyte growth factor c-Met pro-angiogenic factor regulatory T cells gastric cancer targeted therapies Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hepatocyte growth factor c-Met pro-angiogenic factor regulatory T cells gastric cancer targeted therapies Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Juliette Palle Laure Hirsch Alexandra Lapeyre-Prost David Malka Morgane Bourhis Simon Pernot Elie Marcheteau Thibault Voron Florence Castan Ariane Lacotte Nadine Benhamouda Corinne Tanchot Eric François François Ghiringhelli Christelle de la Fouchardière Aziz Zaanan Eric Tartour Julien Taieb Magali Terme Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients
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 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.
format	article
author	Juliette Palle Laure Hirsch Alexandra Lapeyre-Prost David Malka Morgane Bourhis Simon Pernot Elie Marcheteau Thibault Voron Florence Castan Ariane Lacotte Nadine Benhamouda Corinne Tanchot Eric François François Ghiringhelli Christelle de la Fouchardière Aziz Zaanan Eric Tartour Julien Taieb Magali Terme
author_facet	Juliette Palle Laure Hirsch Alexandra Lapeyre-Prost David Malka Morgane Bourhis Simon Pernot Elie Marcheteau Thibault Voron Florence Castan Ariane Lacotte Nadine Benhamouda Corinne Tanchot Eric François François Ghiringhelli Christelle de la Fouchardière Aziz Zaanan Eric Tartour Julien Taieb Magali Terme
author_sort	Juliette Palle
title	Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients
title_short	Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients
title_full	Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients
title_fullStr	Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients
title_full_unstemmed	Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients
title_sort	targeting hgf/c-met axis decreases circulating regulatory t cells accumulation in gastric cancer patients
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c25ad10896804800b263589545bd4b25
work_keys_str_mv	AT juliettepalle targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT laurehirsch targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT alexandralapeyreprost targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT davidmalka targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT morganebourhis targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT simonpernot targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT eliemarcheteau targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT thibaultvoron targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT florencecastan targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT arianelacotte targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT nadinebenhamouda targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT corinnetanchot targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT ericfrancois targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT francoisghiringhelli targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT christelledelafouchardiere targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT azizzaanan targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT erictartour targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT julientaieb targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients AT magaliterme targetinghgfcmetaxisdecreasescirculatingregulatorytcellsaccumulationingastriccancerpatients
_version_	1718435209742909440

Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients

Ejemplares similares