<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">PAPADAKI, MARIA A.</style></author><author><style face="normal" font="default" size="100%">AGGOURAKI, DESPOINA</style></author><author><style face="normal" font="default" size="100%">VETSIKA, ELENI-KYRIAKI</style></author><author><style face="normal" font="default" size="100%">XENIDIS, NIKOLAOS</style></author><author><style face="normal" font="default" size="100%">KALLERGI, GALAKTEA</style></author><author><style face="normal" font="default" size="100%">KOTSAKIS, ATHANASIOS</style></author><author><style face="normal" font="default" size="100%">GEORGOULIAS, VASSILIS</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Epithelial-to-mesenchymal Transition Heterogeneity of Circulating Tumor Cells and Their Correlation With MDSCs and Tregs in HER2-negative Metastatic Breast Cancer Patients</style></title><secondary-title><style face="normal" font="default" size="100%">Anticancer Research</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2021-02-01 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">661-670</style></pages><doi><style  face="normal" font="default" size="100%">10.21873/anticanres.14817</style></doi><volume><style face="normal" font="default" size="100%">41</style></volume><issue><style face="normal" font="default" size="100%">2</style></issue><abstract><style  face="normal" font="default" size="100%">Background: To investigate the correlation between circulating tumor cells (CTCs) bearing cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) phenotypes and the different immunosuppressive cells in peripheral blood of patients with metastatic breast cancer (mBC). Materials and Methods: Blood was obtained from 38 pre-treated patients with mBC before a new line of treatment. CTC detection and characterization was performed by triple immunofluorescent staining, while Myeloid-derived Suppressor Cells (MDSCs) and T regulatory cells (Tregs) were analyzed by multi-flow cytometry. Results: CTCs were detected in 16 (42.1%) of patients. Based on the co-expression of ALDH1, TWIST and CK, CTCs revealed an important heterogeneity: CTCs with a CSC/partial-EMT, CSC/Epithelial-like, non-CSC/partial-EMT and non-CSC/Epithelial-like phenotype were detected in 7 (18.4%), 7 (18.4%), 1 (1.4%) and 9 (23.7%) of patients, respectively. Immunophenotyping of MDSCs identified 2 monocytic [M-MDSCs; CD14+CD15+CD11b+CD33+HLA-DR−Lin− (CD14+CD15+) and CD14+CD15–CD11b+CD33+ HLA-DR−Lin− (CD14+CD15–)] and one granulocytic [G-MDSCs; CD14−CD15+CD11b+CD33+HLA-DR−Lin− (CD14– CD15+)] subpopulations, expressing inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS), respectively. Patients with detectable CTCs had a higher frequency of Tregs (CD3+CD4+CD25high; p=0.022) whereas a positive correlation was found between CTC counts and the percentage of Tregs (p=0.005) and CD14+CD15+ M-MDSCs (p=0.024). Patients with a partial-EMT phenotype had a higher frequency of CD14+CD15+ M-MDSCs (p=0.023). Patients harboring the non-CSC/epithelial-like CTC subpopulation had an increased frequency of CD14-CD15+ G-MDSCs (p=0.020), along with decreased levels of CD3+CD4+CD25high FoxP3+ Tregs (p=0.020). Conclusion: These findings provide evidence that CTCs in ER+/HER2– mBC patients may be under the control of the immune system and various immune escape mechanisms might be involved during the different stages of their biological evolution.</style></abstract></record></records></xml>