Blocking the PD-1/PD-L1 axis enhanced cisplatin chemotherapy in osteosarcoma in vitro and in vivo.
10.1186/s12199-019-0835-3
- Author:
Xiaoqiang LIU
1
;
Shaoya HE
2
;
Huaming WU
3
;
Hui XIE
3
;
Tao ZHANG
4
;
Zhongliang DENG
5
Author Information
1. Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong district, Chongqing, 40010, China.
2. Department of Gastroenterology, Sichuan Anyue County People's Hospital, 68 Wainan Street, Anyue, 642350, China.
3. Department of Orthopedic Surgery, Sichuan Anyue County People's Hospital, 68 Wainan Street, Anyue, 642350, China.
4. Department of orthopedic Surgery, Guizhou Orthopedics Hospital, 123 Shachong South Road, Guiyang, 550002, China.
5. Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong district, Chongqing, 40010, China. dzlbiology@163.com.
- Publication Type:Journal Article
- Keywords:
Anti-PD-1 antibody;
Cisplatin;
Osteosarcoma;
PD-L1;
Treg cell
- From:Environmental Health and Preventive Medicine
2019;24(1):79-79
- CountryJapan
- Language:English
-
Abstract:
BACKGROUND:The blocking of the programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis has been found to have an anticancer activity against various types of cancer by enhancing T cell immunity, while there are no studies linking the PD-1/PD-L1 axis to chemotherapy drugs in osteosarcoma (OS). The present study aimed to investigate the effects of blocking PD-1/PD-L1 axis on the cisplatin chemotherapy in OS in vitro and in vivo.
METHODS:Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to detect PD-L1 mRNA in OS tissues. Cell proliferation and apoptosis were measured by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. In vivo, the syngeneic mice were treated with cisplatin and anti-PD-1 antibody alone or jointly.
RESULTS:In this study, it revealed that PD-L1 mRNA was highly expressed in OS tissues. Further inhibitory evaluation showed that the K7M2-LV cells (PD-L1 overexpression) co-cultured with PD-1 lymphocytes could promote K7M2 cell proliferation. Meanwhile, the combination of anti-PD-1 antibody and cisplatin significantly decreased the proliferation and increased the apoptosis of K7M2 cells in a co-culture system. In vivo, the combination of anti-PD-1 antibody and cisplatin significantly inhibited tumor growth, while the mechanisms did not involve regulatory T cells.
CONCLUSION:The present data suggested that the blocking of PD-1/PD-L1 axis had a positive prognostic value, which can enhance the chemotherapeutic effect of cisplatin in OS. These findings provide a rationale for utilizing PD1/PD-L1 blocking antibodies as a single agent to cure refractory OS in patients receiving cisplatin treatment.
