Siglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients

Aberrant glycosylation actively contributes to tumor progression and is a key hallmark of cancer. Most of the glycan moieties expressed on the surface of cancer cells are sialic acids that may modulate antitumor immune responses via binding to sialic acid–binding immunoglobulin-like lectins (Siglecs...

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Autores principales:	Sulayman Benmerzoug, Mathieu F. Chevalier, Laura Villier, Sylvain Nguyen, Valérie Cesson, Anna K. Schneider, Florence Dartiguenave, Sonia-Christina Rodrigues-Dias, Ilaria Lucca, Patrice Jichlinski, Beat Roth, Denise Nardelli-Haefliger, Laurent Derré
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Bladder cancer Siglec-7 Natural killer cells Immunoregulation Immune checkpoint Diseases of the genitourinary system. Urology RC870-923 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/66cfbf05dc5a4c1abdec773b93fd4a9e
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spelling	oai:doaj.org-article:66cfbf05dc5a4c1abdec773b93fd4a9e2021-11-20T05:13:59ZSiglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients2666-168310.1016/j.euros.2021.10.001https://doaj.org/article/66cfbf05dc5a4c1abdec773b93fd4a9e2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666168321017092https://doaj.org/toc/2666-1683Aberrant glycosylation actively contributes to tumor progression and is a key hallmark of cancer. Most of the glycan moieties expressed on the surface of cancer cells are sialic acids that may modulate antitumor immune responses via binding to sialic acid–binding immunoglobulin-like lectins (Siglecs) expressed by immune cells. Here we show that Siglecs may decrease the bladder tumor immune response mediated by natural killer (NK) cells. We observed higher NK cell activity against desialylated bladder tumor cell lines. We therefore determined the expression of nine Siglecs on circulatory NK cells from healthy donors and patients with bladder cancer (BCa). NK cells from blood mainly express Siglec-7, which is highly upregulated in non–muscle-invasive BCa (NMIBC), as well as Siglec-6, albeit at a much lower level. However, both Siglecs are expressed by urinary NK cells from NMIBC patients undergoing bacillus Calmette-Guérin therapy. Ex vivo analysis of Siglec-6 and Siglec-7 expression levels on tumor-infiltrating NK cells (TINKs) from BCa patients showed that only Siglec-7 is expressed by TINKs. Finally, analyses for The Cancer Genome Atlas data set revealed that BCa patients with high expression levels of Siglec-7 have a poor survival rate. This work indicates that Siglec-7 may restrain NK-mediated antitumor immunity in BCa. Patient summary: We investigated the expression of proteins called Siglecs in natural killer (NK) cells from patients with bladder cancer. We showed that levels of the protein Siglec-7 in blood, urine, and tumors from patients with bladder cancer are associated with poor clinical outcomes. Thus, Siglec-7 may be involved in the regulation of antitumor immunity mediated by NK cells in bladder cancer.Sulayman BenmerzougMathieu F. ChevalierLaura VillierSylvain NguyenValérie CessonAnna K. SchneiderFlorence DartiguenaveSonia-Christina Rodrigues-DiasIlaria LuccaPatrice JichlinskiBeat RothDenise Nardelli-HaefligerLaurent DerréElsevierarticleBladder cancerSiglec-7Natural killer cellsImmunoregulationImmune checkpointDiseases of the genitourinary system. UrologyRC870-923Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENEuropean Urology Open Science, Vol 34, Iss , Pp 79-82 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bladder cancer Siglec-7 Natural killer cells Immunoregulation Immune checkpoint Diseases of the genitourinary system. Urology RC870-923 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Bladder cancer Siglec-7 Natural killer cells Immunoregulation Immune checkpoint Diseases of the genitourinary system. Urology RC870-923 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sulayman Benmerzoug Mathieu F. Chevalier Laura Villier Sylvain Nguyen Valérie Cesson Anna K. Schneider Florence Dartiguenave Sonia-Christina Rodrigues-Dias Ilaria Lucca Patrice Jichlinski Beat Roth Denise Nardelli-Haefliger Laurent Derré Siglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients
description	Aberrant glycosylation actively contributes to tumor progression and is a key hallmark of cancer. Most of the glycan moieties expressed on the surface of cancer cells are sialic acids that may modulate antitumor immune responses via binding to sialic acid–binding immunoglobulin-like lectins (Siglecs) expressed by immune cells. Here we show that Siglecs may decrease the bladder tumor immune response mediated by natural killer (NK) cells. We observed higher NK cell activity against desialylated bladder tumor cell lines. We therefore determined the expression of nine Siglecs on circulatory NK cells from healthy donors and patients with bladder cancer (BCa). NK cells from blood mainly express Siglec-7, which is highly upregulated in non–muscle-invasive BCa (NMIBC), as well as Siglec-6, albeit at a much lower level. However, both Siglecs are expressed by urinary NK cells from NMIBC patients undergoing bacillus Calmette-Guérin therapy. Ex vivo analysis of Siglec-6 and Siglec-7 expression levels on tumor-infiltrating NK cells (TINKs) from BCa patients showed that only Siglec-7 is expressed by TINKs. Finally, analyses for The Cancer Genome Atlas data set revealed that BCa patients with high expression levels of Siglec-7 have a poor survival rate. This work indicates that Siglec-7 may restrain NK-mediated antitumor immunity in BCa. Patient summary: We investigated the expression of proteins called Siglecs in natural killer (NK) cells from patients with bladder cancer. We showed that levels of the protein Siglec-7 in blood, urine, and tumors from patients with bladder cancer are associated with poor clinical outcomes. Thus, Siglec-7 may be involved in the regulation of antitumor immunity mediated by NK cells in bladder cancer.
format	article
author	Sulayman Benmerzoug Mathieu F. Chevalier Laura Villier Sylvain Nguyen Valérie Cesson Anna K. Schneider Florence Dartiguenave Sonia-Christina Rodrigues-Dias Ilaria Lucca Patrice Jichlinski Beat Roth Denise Nardelli-Haefliger Laurent Derré
author_facet	Sulayman Benmerzoug Mathieu F. Chevalier Laura Villier Sylvain Nguyen Valérie Cesson Anna K. Schneider Florence Dartiguenave Sonia-Christina Rodrigues-Dias Ilaria Lucca Patrice Jichlinski Beat Roth Denise Nardelli-Haefliger Laurent Derré
author_sort	Sulayman Benmerzoug
title	Siglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients
title_short	Siglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients
title_full	Siglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients
title_fullStr	Siglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients
title_full_unstemmed	Siglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients
title_sort	siglec-7 may limit natural killer cell–mediated antitumor responses in bladder cancer patients
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/66cfbf05dc5a4c1abdec773b93fd4a9e
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Siglec-7 May Limit Natural Killer Cell–mediated Antitumor responses in Bladder Cancer Patients

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