Application of epirubicin in combination with anti-CD47 antibody for therapy of breast cancer in vitro / 中国免疫学杂志

ABSTRACT

Objective:To explore the effects of combination of epirubicin (EPI) and anti-CD47 antibody on therapy of breast cancer.Calreticulin ( CRT) and CD47 on DC-mediated phagocytosis.Methods: Breast cancer cells MCF-7 and MDA-MB-231 were treated with EPI , and expression of calreticulin ( CRT ) and CD47 on cell surface were detected by flow cytometry or immunofluorescence.DC were isolated from human peripheral blood , and cocultured with epirubicin-treated breast cancer cells in the present of anti-CD47 or anti-CRT antibody ,and the phagocytosis of DC was assessed.Results:Untreated breast cancer cells MCF-7 and MDA-MB-231 did not express CRT on the surface of cells ,but high level of CD47 was detected.After EPI treatment,CRT exposed on the cells surface,and the expression of CD47 was reduced.The results showed that EPI or anti-47 antibody alone increased DC-mediated phagocytosis ,and combination treatment marked enhanced this effects.Further more, in addition of anti-CRT antibody reduced the phagocytosis of DC.Conclusion:EPI could induce CRT exposure on the tumor cell surface ,and enhanced DC-mediated phagocytosis when combination with anti-CD47 antibody.The phagocytosis of DC on tumor cells were modulated by both ecto-CRT and CD47.This study provide a new effective strategy for the use of anti-CD47 antibody among the chemotherapy of breast cancer.