CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse
<p>We 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...
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2019
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| _version_ | 1864513554486394880 |
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| author | Ghina Taouk (14152767) |
| author2 | Ola Hussein (11449275) Moussa Zekak (14152770) Ali Abouelghar (14152773) Yasser Al-Sarraj (11721425) Essam M. Abdelalim (5768072) Manale Karam (14152776) |
| author2_role | author author author author author author |
| author_facet | Ghina Taouk (14152767) Ola Hussein (11449275) Moussa Zekak (14152770) Ali Abouelghar (14152773) Yasser Al-Sarraj (11721425) Essam M. Abdelalim (5768072) Manale Karam (14152776) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ghina Taouk (14152767) Ola Hussein (11449275) Moussa Zekak (14152770) Ali Abouelghar (14152773) Yasser Al-Sarraj (11721425) Essam M. Abdelalim (5768072) Manale Karam (14152776) |
| dc.date.none.fl_str_mv | 2019-06-19T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41598-019-45377-8 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/CD56_expression_in_breast_cancer_induces_sensitivity_to_natural_killer-mediated_cytotoxicity_by_enhancing_the_formation_of_cytotoxic_immunological_synapse/21598125 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Oncology and carcinogenesis Breast cancer Cancer |
| dc.title.none.fl_str_mv | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>We 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.</p><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1038/s41598-019-45377-8" target="_blank">http://dx.doi.org/10.1038/s41598-019-45377-8</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_4add0a3f7938036896cb2cdb4f15a229 |
| identifier_str_mv | 10.1038/s41598-019-45377-8 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/21598125 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapseGhina Taouk (14152767)Ola Hussein (11449275)Moussa Zekak (14152770)Ali Abouelghar (14152773)Yasser Al-Sarraj (11721425)Essam M. Abdelalim (5768072)Manale Karam (14152776)Biomedical and clinical sciencesOncology and carcinogenesisBreast cancerCancer<p>We 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.</p><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1038/s41598-019-45377-8" target="_blank">http://dx.doi.org/10.1038/s41598-019-45377-8</a></p>2019-06-19T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-019-45377-8https://figshare.com/articles/journal_contribution/CD56_expression_in_breast_cancer_induces_sensitivity_to_natural_killer-mediated_cytotoxicity_by_enhancing_the_formation_of_cytotoxic_immunological_synapse/21598125CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/215981252019-06-19T00:00:00Z |
| spellingShingle | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse Ghina Taouk (14152767) Biomedical and clinical sciences Oncology and carcinogenesis Breast cancer Cancer |
| status_str | publishedVersion |
| title | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse |
| title_full | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse |
| title_fullStr | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse |
| title_full_unstemmed | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse |
| title_short | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse |
| title_sort | CD56 expression in breast cancer induces sensitivity to natural killer-mediated cytotoxicity by enhancing the formation of cytotoxic immunological synapse |
| topic | Biomedical and clinical sciences Oncology and carcinogenesis Breast cancer Cancer |