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  • Title: Carboplatin and programmed death-ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model.
    Author: Zhu X, Xu J, Cai H, Lang J.
    Journal: J Obstet Gynaecol Res; 2018 Feb; 44(2):303-311. PubMed ID: 29171115.
    Abstract:
    AIM: In advanced, platinum resistant or refractory ovarian cancer (OC), the therapeutic efficacy of carboplatin is controversial. Although anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway blockages show great potential in cancer treatment, the antitumor effect of single anti-PD-L1 pathway monoclonal antibody (mAb) is not obvious in advanced or some poorly immunogenic tumors, including OC. We compared the effects of single or combined carboplatin and anti-PD-L1 mAb treatments and explored the possible antitumor mechanisms in a murine ID8 OC model. METHODS: C57BL/6 mice with established peritoneal ID8 OC were intraperitoneally injected with single or combined carboplatin and anti-PD-L1 mAb. The formation time of ascites and their overall survival were recorded. The compositions of tumor-associated immune cells were analyzed by flow cytometry. RESULTS: A single treatment of carboplatin and combined carboplatin/PD-L1 mAb induced a strong anti-ascites response. Mice treated with carboplatin presented the longest overall survival, followed by the combined remedy. Mechanistic investigation of the tumor microenvironment revealed that carboplatin and carboplatin/PD-L1 mAb increased antitumor effector CD4+ , CD8+ T cells and decreased immunosuppressive regulatory T and myeloid suppressor cells, giving rise to remarkably higher ratios of effector CD4+ , CD8+ T cells to regulatory T cells and myeloid suppressor cells in the peritoneal cavity. CONCLUSIONS: To our knowledge, this is the first report to compare the antitumor effect and potential mechanisms between carboplatin, PD-L1 mAb and their combination strategies in a murine ID8 OC model. The results of this study may deepen our understanding of OC and aid future preclinical experiments or clinical trials.
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