Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk

Abstract Human leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell function in eliminating malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in peripheral blood. To test the hypothesis that certain KIR-HLA c...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elham Ashouri, Karan Rajalingam, Shaghik Barani, Shirin Farjadian, Abbas Ghaderi, Raja Rajalingam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe0c487a327a468ea88c463c37ad975e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fe0c487a327a468ea88c463c37ad975e
record_format	dspace
spelling	oai:doaj.org-article:fe0c487a327a468ea88c463c37ad975e2021-12-02T18:03:07ZCoexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk10.1038/s41598-021-86964-y2045-2322https://doaj.org/article/fe0c487a327a468ea88c463c37ad975e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86964-yhttps://doaj.org/toc/2045-2322Abstract Human leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell function in eliminating malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in peripheral blood. To test the hypothesis that certain KIR-HLA combinations impairing NK-cytotoxicity predispose to BC risk, we analyzed KIR and HLA polymorphisms in 162 women with BC and 278 controls. KIR-Bx genotypes increased significantly in BC than controls (83.3% vs. 71.9%, OR 1.95), and the increase was more pronounced in advanced-cancer (OR 5.3). No difference was observed with inhibitory KIR (iKIR) and HLA-ligand combinations. The activating KIR (aKIR) and HLA-ligand combinations, 2DS1 + C2 (OR 2.98) and 3DS1 + Bw4 (OR 2.6), were significantly increased in advanced-BC. All patients with advanced-cancer carrying 2DS1 + C2 or 3DS1 + Bw4 also have their iKIR counterparts 2DL1 and 3DL1, respectively. Contrarily, the 2DL1 + C2 and 3DL1 + Bw4 pairs without their aKIR counterparts are significantly higher in controls. These data suggest that NK cells expressing iKIR to the cognate HLA-ligands in the absence of putative aKIR counterpart are instrumental in antitumor response. These data provide a new framework for improving the utility of genetic risk scores for individualized surveillance.Elham AshouriKaran RajalingamShaghik BaraniShirin FarjadianAbbas GhaderiRaja RajalingamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elham Ashouri Karan Rajalingam Shaghik Barani Shirin Farjadian Abbas Ghaderi Raja Rajalingam Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk
description	Abstract Human leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell function in eliminating malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in peripheral blood. To test the hypothesis that certain KIR-HLA combinations impairing NK-cytotoxicity predispose to BC risk, we analyzed KIR and HLA polymorphisms in 162 women with BC and 278 controls. KIR-Bx genotypes increased significantly in BC than controls (83.3% vs. 71.9%, OR 1.95), and the increase was more pronounced in advanced-cancer (OR 5.3). No difference was observed with inhibitory KIR (iKIR) and HLA-ligand combinations. The activating KIR (aKIR) and HLA-ligand combinations, 2DS1 + C2 (OR 2.98) and 3DS1 + Bw4 (OR 2.6), were significantly increased in advanced-BC. All patients with advanced-cancer carrying 2DS1 + C2 or 3DS1 + Bw4 also have their iKIR counterparts 2DL1 and 3DL1, respectively. Contrarily, the 2DL1 + C2 and 3DL1 + Bw4 pairs without their aKIR counterparts are significantly higher in controls. These data suggest that NK cells expressing iKIR to the cognate HLA-ligands in the absence of putative aKIR counterpart are instrumental in antitumor response. These data provide a new framework for improving the utility of genetic risk scores for individualized surveillance.
format	article
author	Elham Ashouri Karan Rajalingam Shaghik Barani Shirin Farjadian Abbas Ghaderi Raja Rajalingam
author_facet	Elham Ashouri Karan Rajalingam Shaghik Barani Shirin Farjadian Abbas Ghaderi Raja Rajalingam
author_sort	Elham Ashouri
title	Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk
title_short	Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk
title_full	Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk
title_fullStr	Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk
title_full_unstemmed	Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk
title_sort	coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate hla-c2 and bw4 ligands confer breast cancer risk
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fe0c487a327a468ea88c463c37ad975e
work_keys_str_mv	AT elhamashouri coexistenceofinhibitoryandactivatingkillercellimmunoglobulinlikereceptorstothesamecognatehlac2andbw4ligandsconferbreastcancerrisk AT karanrajalingam coexistenceofinhibitoryandactivatingkillercellimmunoglobulinlikereceptorstothesamecognatehlac2andbw4ligandsconferbreastcancerrisk AT shaghikbarani coexistenceofinhibitoryandactivatingkillercellimmunoglobulinlikereceptorstothesamecognatehlac2andbw4ligandsconferbreastcancerrisk AT shirinfarjadian coexistenceofinhibitoryandactivatingkillercellimmunoglobulinlikereceptorstothesamecognatehlac2andbw4ligandsconferbreastcancerrisk AT abbasghaderi coexistenceofinhibitoryandactivatingkillercellimmunoglobulinlikereceptorstothesamecognatehlac2andbw4ligandsconferbreastcancerrisk AT rajarajalingam coexistenceofinhibitoryandactivatingkillercellimmunoglobulinlikereceptorstothesamecognatehlac2andbw4ligandsconferbreastcancerrisk
_version_	1718378846507499520

Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk

Ejemplares similares