Cargando…

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

Prediction 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 th...

Descripción completa

Detalles Bibliográficos
Autores principales: Saraiva, Diana P., Jacinto, António, Borralho, Paula, Braga, Sofia, Cabral, M. Guadalupe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282034/
https://www.ncbi.nlm.nih.gov/pubmed/30555458
http://dx.doi.org/10.3389/fimmu.2018.02605
_version_ 1783378914364620800
author Saraiva, Diana P.
Jacinto, António
Borralho, Paula
Braga, Sofia
Cabral, M. Guadalupe
author_facet Saraiva, Diana P.
Jacinto, António
Borralho, Paula
Braga, Sofia
Cabral, M. Guadalupe
author_sort Saraiva, Diana P.
collection PubMed
description Prediction 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-DR(hi) 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.
format Online
Article
Text
id pubmed-6282034
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-62820342018-12-14 HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy Saraiva, Diana P. Jacinto, António Borralho, Paula Braga, Sofia Cabral, M. Guadalupe Front Immunol Immunology Prediction 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-DR(hi) 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. Frontiers Media S.A. 2018-11-13 /pmc/articles/PMC6282034/ /pubmed/30555458 http://dx.doi.org/10.3389/fimmu.2018.02605 Text en Copyright © 2018 Saraiva, Jacinto, Borralho, Braga and Cabral. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Saraiva, Diana P.
Jacinto, António
Borralho, Paula
Braga, Sofia
Cabral, M. Guadalupe
HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy
title HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy
title_full HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy
title_fullStr HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy
title_full_unstemmed HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy
title_short HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy
title_sort hla-dr in cytotoxic t lymphocytes predicts breast cancer patients' response to neoadjuvant chemotherapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282034/
https://www.ncbi.nlm.nih.gov/pubmed/30555458
http://dx.doi.org/10.3389/fimmu.2018.02605
work_keys_str_mv AT saraivadianap hladrincytotoxictlymphocytespredictsbreastcancerpatientsresponsetoneoadjuvantchemotherapy
AT jacintoantonio hladrincytotoxictlymphocytespredictsbreastcancerpatientsresponsetoneoadjuvantchemotherapy
AT borralhopaula hladrincytotoxictlymphocytespredictsbreastcancerpatientsresponsetoneoadjuvantchemotherapy
AT bragasofia hladrincytotoxictlymphocytespredictsbreastcancerpatientsresponsetoneoadjuvantchemotherapy
AT cabralmguadalupe hladrincytotoxictlymphocytespredictsbreastcancerpatientsresponsetoneoadjuvantchemotherapy