The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma

Autores
García, Marcela; Palma, Maria Belen; Verine, Jerome; Miriuka, Santiago Gabriel; Inda, Ana María; Errecalde, Ana Lia; Desgrandchamps, François; Carosella, Edgardo Delfino; Tronik Le Roux, Diana
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4. Methods: Tumor specimens were obtained from patients from two separate cohorts: One from "Evita Pueblo"Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR. Results: Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased. Conclusions: In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.
Fil: García, Marcela. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina
Fil: Palma, Maria Belen. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Verine, Jerome. Ap-hp, Saint-louis Hospital; Francia. Research Division in Hematology and Immunology; Francia
Fil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Inda, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina
Fil: Errecalde, Ana Lia. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina
Fil: Desgrandchamps, François. Saint-louis Hospital; Francia
Fil: Carosella, Edgardo Delfino. Universite de Paris; Francia
Fil: Tronik Le Roux, Diana. Universite de Paris; Francia
Materia
ANGIOGENESIS
CCRCC
HLA-G
ILT4
IMMUNE-THERAPY
LYMPHANGIOGENESIS
VEGF
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/169404
Acceder
id CONICETDig_f66804a1348783414cdeadb77b713aa5
oai_identifier_str oai:ri.conicet.gov.ar:11336/169404
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinomaGarcía, MarcelaPalma, Maria BelenVerine, JeromeMiriuka, Santiago GabrielInda, Ana MaríaErrecalde, Ana LiaDesgrandchamps, FrançoisCarosella, Edgardo DelfinoTronik Le Roux, DianaANGIOGENESISCCRCCHLA-GILT4IMMUNE-THERAPYLYMPHANGIOGENESISVEGFhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4. Methods: Tumor specimens were obtained from patients from two separate cohorts: One from "Evita Pueblo"Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR. Results: Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased. Conclusions: In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.Fil: García, Marcela. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; ArgentinaFil: Palma, Maria Belen. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Verine, Jerome. Ap-hp, Saint-louis Hospital; Francia. Research Division in Hematology and Immunology; FranciaFil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inda, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; ArgentinaFil: Errecalde, Ana Lia. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; ArgentinaFil: Desgrandchamps, François. Saint-louis Hospital; FranciaFil: Carosella, Edgardo Delfino. Universite de Paris; FranciaFil: Tronik Le Roux, Diana. Universite de Paris; FranciaBioMed Central2020-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/169404García, Marcela; Palma, Maria Belen; Verine, Jerome; Miriuka, Santiago Gabriel; Inda, Ana María; et al.; The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma; BioMed Central; BMC Cancer; 20; 1; 7-2020; 1-111471-2407CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07113-8info:eu-repo/semantics/altIdentifier/doi/10.1186/s12885-020-07113-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:46:05Zoai:ri.conicet.gov.ar:11336/169404instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:46:05.513CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
title The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
spellingShingle The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
García, Marcela
ANGIOGENESIS
CCRCC
HLA-G
ILT4
IMMUNE-THERAPY
LYMPHANGIOGENESIS
VEGF
title_short The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
title_full The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
title_fullStr The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
title_full_unstemmed The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
title_sort The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
dc.creator.none.fl_str_mv García, Marcela
Palma, Maria Belen
Verine, Jerome
Miriuka, Santiago Gabriel
Inda, Ana María
Errecalde, Ana Lia
Desgrandchamps, François
Carosella, Edgardo Delfino
Tronik Le Roux, Diana
author García, Marcela
author_facet García, Marcela
Palma, Maria Belen
Verine, Jerome
Miriuka, Santiago Gabriel
Inda, Ana María
Errecalde, Ana Lia
Desgrandchamps, François
Carosella, Edgardo Delfino
Tronik Le Roux, Diana
author_role author
author2 Palma, Maria Belen
Verine, Jerome
Miriuka, Santiago Gabriel
Inda, Ana María
Errecalde, Ana Lia
Desgrandchamps, François
Carosella, Edgardo Delfino
Tronik Le Roux, Diana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOGENESIS
CCRCC
HLA-G
ILT4
IMMUNE-THERAPY
LYMPHANGIOGENESIS
VEGF
topic ANGIOGENESIS
CCRCC
HLA-G
ILT4
IMMUNE-THERAPY
LYMPHANGIOGENESIS
VEGF
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4. Methods: Tumor specimens were obtained from patients from two separate cohorts: One from "Evita Pueblo"Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR. Results: Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased. Conclusions: In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.
Fil: García, Marcela. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina
Fil: Palma, Maria Belen. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Verine, Jerome. Ap-hp, Saint-louis Hospital; Francia. Research Division in Hematology and Immunology; Francia
Fil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Inda, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina
Fil: Errecalde, Ana Lia. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina
Fil: Desgrandchamps, François. Saint-louis Hospital; Francia
Fil: Carosella, Edgardo Delfino. Universite de Paris; Francia
Fil: Tronik Le Roux, Diana. Universite de Paris; Francia
description Background: Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4. Methods: Tumor specimens were obtained from patients from two separate cohorts: One from "Evita Pueblo"Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR. Results: Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased. Conclusions: In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.
publishDate 2020
dc.date.none.fl_str_mv 2020-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/169404
García, Marcela; Palma, Maria Belen; Verine, Jerome; Miriuka, Santiago Gabriel; Inda, Ana María; et al.; The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma; BioMed Central; BMC Cancer; 20; 1; 7-2020; 1-11
1471-2407
CONICET Digital
CONICET
url http://hdl.handle.net/11336/169404
identifier_str_mv García, Marcela; Palma, Maria Belen; Verine, Jerome; Miriuka, Santiago Gabriel; Inda, Ana María; et al.; The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma; BioMed Central; BMC Cancer; 20; 1; 7-2020; 1-11
1471-2407
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07113-8
info:eu-repo/semantics/altIdentifier/doi/10.1186/s12885-020-07113-8
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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