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المؤلفTaouk G.
المؤلفHussein O.
المؤلفZekak M.
المؤلفAbouelghar A.
المؤلفAl-Sarraj Y.
المؤلفAbdelalim E.M.
المؤلفKaram M.
تاريخ الإتاحة2020-04-01T06:59:42Z
تاريخ النشر2019
اسم المنشورScientific Reports
المصدرScopus
الرقم المعياري الدولي للكتاب20452322
معرّف المصادر الموحدhttp://dx.doi.org/10.1038/s41598-019-45377-8
معرّف المصادر الموحدhttp://hdl.handle.net/10576/13674
الملخصWe examined the potential value of the natural killer (NK) cell line; NK-92, as immunotherapy tool for breast cancer (BC) treatment and searched for biomarker(s) of sensitivity to NK-92-mediated cytotoxicity. The cytotoxic activity of NK-92 cells towards one breast precancerous and nine BC cell lines was analyzed using calcein-AM and degranulation assays. The molecules associated with NK-92-responsiveness were determined by differential gene expression analysis using RNA-sequencing and validated by RT-PCR, immunostaining and flow cytometry. NK-target interactions and immunological synapse formation were assessed by fluorescence microscopy. Potential biomarker expression was determined by IHC in 99 patient-derived BC tissues and 10 normal mammary epithelial tissues. Most (8/9) BC cell lines were resistant while only one BC and the precancerous cell lines were effectively killed by NK-92 lymphocytes. NK-92-sensitive target cells specifically expressed CD56, which ectopic expression in CD56-negative BC cells induced their sensitivity to NK-92-mediated killing, suggesting that CD56 is not only a biomarker of responsiveness but actively regulates NK function. CD56 adhesion molecules which are also expressed on NK cells accumulate at the immunological synapse enhancing NK-target interactions, cytotoxic granzyme B transfer from NK-92 to CD56-expressing target cells and induction of caspase 3 activation in targets. Interestingly, CD56 expression was found to be reduced in breast tumor tissues (36%) with strong inter- and intratumoral heterogeneity in comparison to normal breast tissues (80%). CD56 is a potential predictive biomarker for BC responsiveness to NK-92-cell based immunotherapy and loss of CD56 expression might be a mechanism of escape from NK-immunity. - 2019, The Author(s).
راعي المشروعWe would like to thank Ms Khaoula Errafii, Dr Kumaran Mande and Dr Richard Thompson for technical support in RNA sequencing. This work was supported by the Qatar Biomedical Research Institute (QBRI), Qatar Foundation.
اللغةen
الناشرNature Publishing Group
الموضوعKiller Cells, Natural
Neoplasms
Immunotherapy
العنوانCD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse
النوعArticle
رقم العدد1
رقم المجلد9
dc.accessType Open Access


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