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HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy

dc.contributor.authorSaraiva, DP
dc.contributor.authorJacinto, A
dc.contributor.authorBorralho, P
dc.contributor.authorBraga, S
dc.contributor.authorCabral, MG
dc.date.accessioned2019-01-09T23:20:41Z
dc.date.available2019-01-09T23:20:41Z
dc.date.issued2018
dc.description.abstractPrediction of breast cancer response to Neoadjuvant Chemotherapy (NACT) is an urgent need to promptly direct non-responder patients to alternative therapies. Infiltrating T lymphocytes, namely cytotoxic T lymphocytes (CTLs) have been appointed as predictors of response. However, cancer cells have the ability to dampen CTLs' activity and thus, the prognostic value of the CTLs, per se, is debatable. Here, we disclose that more than the occurrence of CTLs, it is their activation state, revealed by HLA-DR expression, that can accurately predict response to NACT. Flow cytometry analysis of breast cancer biopsies showed that the frequency of CTLs and other lymphocytes were similar regardless disease stage and between NACT responders and non-responders. However, only breast cancer patients without axillary lymph node metastasis and NACT responders have HLA-DRhi CTLs. Interestingly, HLA-DR levels in tumor CTLs is correlated with HLA-DR levels in systemic CTLs. These HLA-DR+ CTLs produce IFN-γ and Granzyme B, enlightening their effector and probable anti-tumor activity profile. Moreover, the level of HLA-DR in CTLs is negatively correlated with the level of HLA-DR in T regulatory lymphocytes and with immunosuppressive and pro-tumor molecules in the tumor microenvironment. Hence, HLA-DR levels in CTLs is a highly sensitive and specific potential predictive factor of NACT-response, which can be assessed in blood to guide therapeutic decisions.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Immunol. 2018 Nov 13;9:2605.pt_PT
dc.identifier.doi10.3389/fimmu.2018.02605pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.26/25642
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectNeoplasias da Mamapt_PT
dc.subjectTerapia Neoadjuvantept_PT
dc.subjectLinfócitos T Citotóxicospt_PT
dc.subjectAntígenos HLA-DRpt_PT
dc.subjectHLA-DR Antigenspt_PT
dc.subjectNeoadjuvant Therapypt_PT
dc.subjectT-Lymphocytes, Cytotoxicpt_PT
dc.subjectBreast Neoplasmspt_PT
dc.titleHLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage2605pt_PT
oaire.citation.volume9pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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