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

• Published in: Frontiers in immunology Vol. 9; p. 2605
• Main Authors: Saraiva, Diana P, Jacinto, António, Borralho, Paula, Braga, Sofia, Cabral, M Guadalupe
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 13-11-2018
• Subjects: Adult; Aged; Aged, 80 and over; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Cell Line; cytotoxic T lymphocytes; Female; Granzymes - pharmacology; HLA-DR; HLA-DR Antigens - immunology; Humans; Immunology; Interferon-gamma - immunology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphatic Metastasis - immunology; Middle Aged; neoadjuvant chemotherapy; Neoadjuvant Therapy - methods; prediction; Prognosis; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; prediction; neoadjuvant chemotherapy; breast cancer; cytotoxic T lymphocytes; HLA-DR
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.02605

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,
, 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
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.