Blockade pf CD73/adenosine axis improves the therapeutic efficacy of docetaxel in epithelial ovarian cancer
Epithelial ovarian cancer (EOC) is the most common and lethal ovarian cancer which threatens women health. Nowadays, the standard treatment is maximal cytoreductive surgical debulking followed by chemotherapy. However, immunosuppressive environment generated by chemotherapy, which can be reversed by immunotherapy, leads to the failure of standard treatment. Therefore, a combination of chemotherapy and immunotherapy will be a promising strategy for EOC patients.
For in vitro study, CD73 expression, CD73 activity, and CD8+ T-cell proliferation were measured after docetaxel (DTXL) treatment with or without CD73 antibody. For in vivo study, tumor growth, tumor weight, and the population of various immune cells in the tumor were analyzed in different drug treatment groups.
DTXL can increase both the CD73 expression and enzymatic activity in patient-derived epithelial cell and ID8 cell while causing immunosuppressive response which was reversed by anti-CD73 antibody (aCD73). Moreover, tumor growth and lung metastasis in mouse were significantly diminished after DTXL + aCD73 treatment.
Blocking CD73/adenosine pathway could reverse the immunosuppression caused by DTXL, and a combination of DTXL with CD73 inhibitor or anti-CD73 antibody would be a more effective and promising therapy for EOC.
KeywordsEpithelial ovarian cancer Docetaxel CD73 Chemotherapy Patient-derived cancer cell
Data collection and analysis: HL, ML, BQ, and XL; study designed and manuscript writing: XL. All authors approved the final submission.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest to disclose.
Research involving human participants and/or animals
Human study was approved by the Ethical Committee in Heze Municipal Hospital of Shandong Province. All animal studies were in accordance with Guide for the Care and Use of Laboratory Animals (8th edition, NIH), and approved by the Institutional Animal Care and Use Committee in Heze Municipal Hospital of Shandong Province.
Written consent was derived from the participants.
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