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

Cancers

Ana Antunes¹  Sofia Azeredo-Lopes²  Zita Seabra³  Isabel L. Pereira⁴  Paula Borralho⁴  Ida Negreiros⁴  Beatriz Assis⁴  Sofia Braga⁵  M. Guadalupe Cabral⁵  Diana P. Saraiva⁵  António Jacinto⁵  Rute Salvador⁵ 

[1] CHRC, CEDOC, NOVA Medical School (NMS), Universidade Nova de Lisboa, 1150-082 Lisbon, Portugal;Public Health and Biostatistics Department, NOVA Medical School (NMS), Universidade Nova de Lisboa, 1150-082 Lisbon, Portugal;Unidade de Imagiologia, Hospital Vila Franca de Xira, 2600-009 Vila Franca de Xira, Portugal;Unidade de Mama, Instituto CUF de Oncologia, 1998-018 Lisbon, Portugal;iNOVA4Health, CEDOC, NOVA Medical School (NMS), Universidade Nova de Lisboa, 1150-082 Lisbon, Portugal;

关键词: breast cancer;    cytotoxic T lymphocytes;    HLA-DR;    biomarker;    neoadjuvant chemotherapy;    3D co-cultures;   

DOI  :  10.3390/cancers13153841

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown