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Carboplatin and programmed death‐ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID 8 ovarian cancer model
Author(s) -
Zhu Xinxin,
Xu Jia,
Cai Han,
Lang Jinghe
Publication year - 2018
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.13521
Subject(s) - carboplatin , medicine , cancer research , monoclonal antibody , cd8 , ovarian cancer , blockade , pharmacology , cancer , immunology , immune system , antibody , chemotherapy , receptor , cisplatin
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 ‐ L 1) pathway blockages show great potential in cancer treatment, the antitumor effect of single anti‐ PD ‐ L 1 pathway monoclonal antibody (m A b) is not obvious in advanced or some poorly immunogenic tumors, including OC. We compared the effects of single or combined carboplatin and anti‐ PD ‐ L 1 m A b treatments and explored the possible antitumor mechanisms in a murine ID 8 OC model. Methods C 57 BL /6 mice with established peritoneal ID 8 OC were intraperitoneally injected with single or combined carboplatin and anti‐ PD ‐ L 1 m A b. 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 ‐ L 1 m A b 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 ‐ L 1 m A b increased antitumor effector CD 4 + , CD 8 + T cells and decreased immunosuppressive regulatory T and myeloid suppressor cells, giving rise to remarkably higher ratios of effector CD 4 + , CD 8 + 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 ‐ L 1 m A b and their combination strategies in a murine ID 8 OC model. The results of this study may deepen our understanding of OC and aid future preclinical experiments or clinical trials.