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Saraiva DP, Azeredo-Lopes S, Antunes A, et al. Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancer. Cancers (Basel). 2021;13(15)doi: 10.3390/cancers13153841.
Saraiva, D. P., Azeredo-Lopes, S., Antunes, A., Salvador, R., Borralho, P., Assis, B., Pereira, I. L., Seabra, Z., Negreiros, I., Jacinto, A., Braga, S., & Cabral, M. G. (2021). Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancer. Cancers, 13(15), . https://doi.org/10.3390/cancers13153841
Saraiva, Diana P, et al. "Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancer." Cancers vol. 13,15 (2021). doi: https://doi.org/10.3390/cancers13153841
Saraiva DP, Azeredo-Lopes S, Antunes A, Salvador R, Borralho P, Assis B, Pereira IL, Seabra Z, Negreiros I, Jacinto A, Braga S, Cabral MG. Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancer. Cancers (Basel). 2021 Jul 30;13(15). doi: 10.3390/cancers13153841. PMID: 34359741; PMCID: PMC8345089.
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Cancers (Basel). 2021 Jul 30;13(15). doi: 10.3390/cancers13153841.

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

Cancers

Diana P Saraiva, Sofia Azeredo-Lopes, Ana Antunes, Rute Salvador, Paula Borralho, Beatriz Assis, Isabel L Pereira, Zita Seabra, Ida Negreiros, António Jacinto, Sofia Braga, M Guadalupe Cabral

Affiliations

  1. iNOVA4Health, CEDOC, NOVA Medical School (NMS), Universidade Nova de Lisboa, 1150-082 Lisbon, Portugal.
  2. Public Health and Biostatistics Department, NOVA Medical School (NMS), Universidade Nova de Lisboa, 1150-082 Lisbon, Portugal.
  3. CHRC, CEDOC, NOVA Medical School (NMS), Universidade Nova de Lisboa, 1150-082 Lisbon, Portugal.
  4. Unidade de Mama, Instituto CUF de Oncologia, 1998-018 Lisbon, Portugal.
  5. Instituto de Anatomia Patológica, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisbon, Portugal.
  6. Unidade de Imagiologia, Hospital Vila Franca de Xira, 2600-009 Vila Franca de Xira, Portugal.

PMID: 34359741 PMCID: PMC8345089 DOI: 10.3390/cancers13153841

Abstract

Neoadjuvant 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.

Keywords: 3D co-cultures; HLA-DR; biomarker; breast cancer; cytotoxic T lymphocytes; immune-modulation; neoadjuvant chemotherapy

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