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

Autor:	Shirin Farjadian, Shaghik Barani, Elham Ashouri, Abbas Ghaderi, Karan Rajalingam, Raja Rajalingam
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	0301 basic medicine Heterozygote Science Cell Immunology Breast Neoplasms Human leukocyte antigen HLA-C Antigens Biology Inhibitory postsynaptic potential Malignancy Ligands Article 03 medical and health sciences 0302 clinical medicine Breast cancer Medical research Receptors KIR Risk Factors Genotype Receptors Breast Cancer medicine 2.1 Biological and endogenous factors Humans Aetiology Receptor Neoplasm Staging Cancer Multidisciplinary medicine.disease KIR 030104 developmental biology medicine.anatomical_structure Haplotypes Oncology Risk factors HLA-B Antigens 030220 oncology & carcinogenesis Case-Control Studies Cancer research biology.protein Medicine Female Antibody
Zdroj:	Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) Scientific Reports Scientific reports, vol 11, iss 1
ISSN:	2045-2322
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::29f5560c234cc3f449d3c8516840d870 https://doaj.org/article/fe0c487a327a468ea88c463c37ad975e Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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