期刊
BMC CANCER
卷 18, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12885-017-3982-1
关键词
Breast cancer; Chemotherapy; Neoadjuvant; T cells; Dendritic cells; Doxorubicin; Immune-monitoring
类别
资金
- Direccion de Investigacion de Bogota (DIB)-HERMES Grants from the Universidad Nacional de Colombia [33317, 23791, 33290, 32181, 21275, 19058, 18458, 14976, 13245, 12543, 11748]
- Fundacion Salud de Los Andes [110150227509]
- COLCIENCIAS [110150227509]
- Fundacion Salud de Los Andes, Bogota-Colombia South America
Background: Vaccination of mice with tumors treated with Doxorubicin promotes a T cell immunity that relies on dendritic cell (DC) activation and is responsible for tumor control in vaccinated animals. Despite Doxorubicin in combination with Cyclophosphamide (A/C) is widely used to treat breast cancer patients, the stimulating effect of A/C on T and APC compartments and its correlation with patient's clinical response remains to be proved. Methods: In this prospective study, we designed an in vitro system to monitor various immunological readouts in PBMCs obtained from a total of 17 breast cancer patients before, and after neoadjuvant anti-tumor therapy with A/C. Results: The results show that before treatment, T cells and DCs, exhibit a marked unresponsiveness to in vitro stimulus: whereas T cells exhibit poor TCR internalization and limited expression of CD154 in response to anti-CD3/CD28/CD2 stimulation, DCs secrete low levels of IL-12p70 and limited CD83 expression in response to pro-inflammatory cytokines. Notably, after treatment the responsiveness of T and APC compartments was recovered, and furthermore, this recovery correlated with patients' residual cancer burden stage. Conclusions: Our results let us to argue that the model used here to monitor the T and APC compartments is suitable to survey the recovery of immune surveillance and to predict tumor response during A/C chemotherapy.
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