Open AccessB7-H3 on circulating epithelial tumor cells correlates with the proliferation marker, Ki-67, and may be associated with the aggressiveness of tumors in breast cancer patients
Author(s) -
Monika Pizon,
Dorothea Schott,
Ulrich Pachmann,
Katharina Pachmann
Publication year - 2018
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2018.4551
Subject(s) - breast cancer , cancer , oncogene , molecular medicine , immune checkpoint , immune system , cell cycle , biomarker , medicine , immunohistochemistry , ki 67 , oncology , cancer research , immunology , biology , immunotherapy , biochemistry
Circulating epithelial tumor cells (CETCs) in peripheral blood are a prerequisite for the development of metastases. B7-H3 is an important immune checkpoint member of the B7 family and inhibits T-cell mediated antitumor immunity. Its expression is associated with a negative prognosis and a poor clinical outcome. Based on the clinical success of inhibitory immune checkpoint blockade, monoclonal antibodies (mAbs) against B7-H3 appear to be a promising therapeutic strategy. The proliferation biomarker, Ki-67, is used as a prognostic factor for breast cancer and reflects the proliferative potential of the tumor. In order to better understand the role of B7-H3 and Ki-67 in cancer development, in this study, we used a real-time biopsy for determining both biomarkers on CETCs in breast cancer patients. Blood from 50 patients suffering from breast cancer was analyzed for CETCs and the expression of B7-H3 and Ki-67 using the maintrac® method. B7-H3 expression on CETCs was found in 82% of the patients. The frequency of B7-H3- and Ki-67‑positive CETCs was significantly higher in patients who had received radiation therapy compared to patients who had not received irradiation. B7-H3‑positive CETCs seemed to be more aggressive as the percentage of B7-H3‑positive CETCs correlated with the percentage of cells positive for the proliferation marker, Ki-67 (r=0.72 P<0.001). A significant association between the Ki-67 and B7-H3 expression level on the CETCs and nodal status was observed. On the whole, the findings of this study indicate that breast cancer patients have detectable CETCs with a high frequency of B7-H3 expression regardless of the stage of the disease. B7-H3 seems to be an important factor in immune evasion and may thus be a promising target for anticancer therapies. Radiation may lead to an upregulation of B7-H3 expression on CETCs, which could be a possible mechanism of acquired radio-resistance.