Circulating regulatory T cells from breast cancer patients in response to neoadjuvant chemotherapy

Background: Immune escape of tumor cells is a new hallmark of cancer in general, and breast cancer, in particular. Previous studies have demonstrated that the immunological profile in peripheral blood may be a prognostic and/or predictive biomarker in breast cancer. Thus, higher number of regulatory T cells (Tregs) in blood from patients with breast cancer has been reported in relation to normal donors. In the present study, we planned to evaluate the changes in different cell populations in peripheral blood: neutrophils, monocytes and lymphocytes, as well as lymphocyte subpopulations [natural killer (NK), B lymphocytes, T lymphocytes, both CD4(+) and CD8(+), and Tregs] from patients with local breast cancer (both Her2(+) and Her2(-)), before, during and after neoadjuvant chemotherapy. Methods: We have employed flow cytometry for the cell analysis of fresh samples obtained before and whilst the neoadjuvant treatment was accomplished. We have studied 50 successive patients from the Breast Cancer Unit of the Virgen Macarena University Hospital during 2 years. Results: Neoadjuvant chemotherapy induced a significant reduction in B cells, especially in Her2(-) patients, and a reduction in NK cells. CD4(+) T cells decreased, whereas CD8(+) cells only decreased in Her2(-) patients. Tregs were also diminished, especially in Her2(+) patients, in response to treatment. Thus, higher CD8/Treg ratio was observed in Her2(+) patients. A higher percentage of Her2(+) patients (66.6%) achieved complete response than Her2(-) patients (27.5%). Monocytes and neutrophils were not changed in peripheral blood. Conclusions: Even though the decrease in B cells and NK cells in response to chemotherapy may be deleterious in the neoadjuvant treatment of breast cancer, the decrease in Tregs and CD4 T cells, but not CD8 T cells, increasing the CD8/Treg ratio, especially in Her2(+) patients, may reveal a new tool to monitor the immune response in breast cancer treated with chemotherapy in the neoadjuvant setting.