Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD4...

Autores: Ziblat, Andrea; Raffo Iraolagoitia, Ximena Lucía; Nuñez, Sol Yanel; Torres, Nicolás; Secchiari, Florencia; Sierra, Jessica Mariel; Spallanzani, Raúl Germán; Rovegno, Agustín; Secin, Fernando Pablo; Fuertes, Mercedes Beatriz; Domaica, Carolina Ines; Zwirner, Norberto Walter
Año de publicación: 2021
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j+ and PD-1+ cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients.
Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Nuñez, Sol Yanel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sierra, Jessica Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Spallanzani, Raúl Germán. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rovegno, Agustín. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina
Fil: Secin, Fernando Pablo. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina
Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Materia: CD45
CD48
CD85J
NK CELLS
PD-1
RENAL CELL CARCINOMA
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/140164

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repository_id_str	3498
network_name_str	CONICET Digital (CONICET)
spelling	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1Ziblat, AndreaRaffo Iraolagoitia, Ximena LucíaNuñez, Sol YanelTorres, NicolásSecchiari, FlorenciaSierra, Jessica MarielSpallanzani, Raúl GermánRovegno, AgustínSecin, Fernando PabloFuertes, Mercedes BeatrizDomaica, Carolina InesZwirner, Norberto WalterCD45CD48CD85JNK CELLSPD-1RENAL CELL CARCINOMAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j+ and PD-1+ cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients.Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nuñez, Sol Yanel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sierra, Jessica Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Spallanzani, Raúl Germán. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rovegno, Agustín. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Secin, Fernando Pablo. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFrontiers Media S.A.2021-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/140164Ziblat, Andrea; Raffo Iraolagoitia, Ximena Lucía; Nuñez, Sol Yanel; Torres, Nicolás; Secchiari, Florencia; et al.; Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1; Frontiers Media S.A.; Frontiers in Immunology; 12; 6-20211664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2021.681615/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2021.681615info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:44:54Zoai:ri.conicet.gov.ar:11336/140164instacron: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:34982025-09-29 10:44:55.1CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1
title	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1
spellingShingle	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1 Ziblat, Andrea CD45 CD48 CD85J NK CELLS PD-1 RENAL CELL CARCINOMA
title_short	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1
title_full	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1
title_fullStr	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1
title_full_unstemmed	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1
title_sort	Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1
dc.creator.none.fl_str_mv	Ziblat, Andrea Raffo Iraolagoitia, Ximena Lucía Nuñez, Sol Yanel Torres, Nicolás Secchiari, Florencia Sierra, Jessica Mariel Spallanzani, Raúl Germán Rovegno, Agustín Secin, Fernando Pablo Fuertes, Mercedes Beatriz Domaica, Carolina Ines Zwirner, Norberto Walter
author	Ziblat, Andrea
author_facet	Ziblat, Andrea Raffo Iraolagoitia, Ximena Lucía Nuñez, Sol Yanel Torres, Nicolás Secchiari, Florencia Sierra, Jessica Mariel Spallanzani, Raúl Germán Rovegno, Agustín Secin, Fernando Pablo Fuertes, Mercedes Beatriz Domaica, Carolina Ines Zwirner, Norberto Walter
author_role	author
author2	Raffo Iraolagoitia, Ximena Lucía Nuñez, Sol Yanel Torres, Nicolás Secchiari, Florencia Sierra, Jessica Mariel Spallanzani, Raúl Germán Rovegno, Agustín Secin, Fernando Pablo Fuertes, Mercedes Beatriz Domaica, Carolina Ines Zwirner, Norberto Walter
author2_role	author author author author author author author author author author author
dc.subject.none.fl_str_mv	CD45 CD48 CD85J NK CELLS PD-1 RENAL CELL CARCINOMA
topic	CD45 CD48 CD85J NK CELLS PD-1 RENAL CELL CARCINOMA
purl_subject.fl_str_mv	https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv	Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j+ and PD-1+ cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients. Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Nuñez, Sol Yanel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Sierra, Jessica Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Spallanzani, Raúl Germán. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Rovegno, Agustín. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina Fil: Secin, Fernando Pablo. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
description	Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j+ and PD-1+ cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients.
publishDate	2021
dc.date.none.fl_str_mv	2021-06
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/11336/140164 Ziblat, Andrea; Raffo Iraolagoitia, Ximena Lucía; Nuñez, Sol Yanel; Torres, Nicolás; Secchiari, Florencia; et al.; Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1; Frontiers Media S.A.; Frontiers in Immunology; 12; 6-2021 1664-3224 CONICET Digital CONICET
url	http://hdl.handle.net/11336/140164
identifier_str_mv	Ziblat, Andrea; Raffo Iraolagoitia, Ximena Lucía; Nuñez, Sol Yanel; Torres, Nicolás; Secchiari, Florencia; et al.; Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD45, CD48 and PD-1; Frontiers Media S.A.; Frontiers in Immunology; 12; 6-2021 1664-3224 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://www.frontiersin.org/articles/10.3389/fimmu.2021.681615/full info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2021.681615
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	Frontiers Media S.A.
publisher.none.fl_str_mv	Frontiers Media S.A.
dc.source.none.fl_str_mv	reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str	CONICET Digital (CONICET)
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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	13.070432

Circulating and tumor-infiltrating NK cells from clear cell renal cell carcinoma patients exhibit a predominantly inhibitory phenotype characterized by overexpression of CD85j, CD4...

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