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Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancer

2021Journal article Open access
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dc.contributor.authorSaraiva, DP
dc.contributor.authorAzeredo-Lopes, S
dc.contributor.authorAntunes, A
dc.contributor.authorSalvador, R
dc.contributor.authorBorralho, P
dc.contributor.authorAssis, B
dc.contributor.authorPereira, IL
dc.contributor.authorSeabra, Z
dc.contributor.authorNegreiros, I
dc.contributor.authorJacinto, A
dc.contributor.authorBraga, S
dc.contributor.authorCabral, MG
dc.date.accessioned2021-08-24T20:50:10Z
dc.date.available2021-08-24T20:50:10Z
dc.date.issued2021
dc.description.abstractNeoadjuvant chemotherapy (NACT) is common in breast cancer (BC) treatment, though more than half of the patients lack an effective response. Therefore, new predictive biomarkers and alternative therapies are crucial. Previously, we proposed HLA-DR-expressing cytotoxic T lymphocytes (CTLs) as a potential biomarker of the response to NACT. To validate this observation and further investigate these cells, 202 BC patients were enrolled. Flow cytometry analyses were performed in 61 biopsies and 41 blood samples pre-NACT and 100 non-NACT tumor samples. All the patients were followed up for 34 months. Blood-isolated immune cells were cultured with BC cell lines in a 3D system. We confirmed that HLA-DR level in CTLs is a highly sensitive, specific, and independent biomarker to predict response to NACT and developed a predictive probability model. This biomarker was also associated with progression-free survival, regardless of the treatment. The clinical observations are substantiated by the anti-tumor properties of HLA-DR-expressing CTLs. Intriguingly, HLA-DR level in CTLs can be modulated ex vivo, boosting their capacity to kill tumor cells synergistically with doxorubicin. Thus, HLA-DR expression in CTLs is a validated tool to select patients that will actually benefit from NACT, and its stimulation might be a novel therapeutic approach for BC.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCancers (Basel) . 2021 Jul 30;13(15):3841pt_PT
dc.identifier.doi10.3390/cancers13153841pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.26/37360
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationDoctoral Program in Bioengineering - Cell Therapies and Regenerative Medicine - Translating Breast Cancer Immune Features Into Targeted Therapies
dc.relationExploring the antitumor effect of HLA-DR+ Cytotoxic T Lymphocytes in prognosis and treatment of Breast Cancer
dc.subjectBiomarcadores Tumoraispt_PT
dc.subjectLinfócitos do Interstício Tumoralpt_PT
dc.subjectTerapia Neoadjuvantept_PT
dc.subjectNeoplasias da Mamapt_PT
dc.subjectBreast Neoplasmspt_PT
dc.subjectBiomarkers, Tumorpt_PT
dc.subjectLymphocytes, Tumor-Infiltratingpt_PT
dc.subjectNeoadjuvant Therapypt_PT
dc.titleExpression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDoctoral Program in Bioengineering - Cell Therapies and Regenerative Medicine - Translating Breast Cancer Immune Features Into Targeted Therapies
oaire.awardTitleExploring the antitumor effect of HLA-DR+ Cytotoxic T Lymphocytes in prognosis and treatment of Breast Cancer
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F114023%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F148422%2F2019/PT
oaire.citation.issue15pt_PT
oaire.citation.startPage3841pt_PT
oaire.citation.titleCancerspt_PT
oaire.citation.volume13pt_PT
oaire.fundingStreamOE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationaa7082f6-92c8-4cd9-acca-d515de7a741a
relation.isProjectOfPublication4690bd48-3c4c-4d32-a7a7-6804e8c0fd5e
relation.isProjectOfPublication.latestForDiscovery4690bd48-3c4c-4d32-a7a7-6804e8c0fd5e

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