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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Blocking the PD-1/PD-L1 axis enhanced cisplatin chemotherapy in osteosarcoma in vitro and in vivo
Xiaoqiang Liu1,2, Shaoya He3, Huaming Wu2
1Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong district, Chongqing, 40010, China.
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.
Insights
Blocking the programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis enhances cisplatin chemotherapy in osteosarcoma (OS). This combination therapy reduces tumor growth and increases cancer cell death, offering a new strategy for refractory OS.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- The programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis plays a role in cancer immunity.
- Limited research exists on the PD-1/PD-L1 axis in osteosarcoma (OS) chemotherapy.
- This study investigates the combined effects of PD-1/PD-L1 axis blockade and cisplatin in OS.
Purpose of the Study:
- To evaluate the impact of blocking the PD-1/PD-L1 axis on cisplatin chemotherapy efficacy in osteosarcoma.
- To explore the potential of this combination therapy in both in vitro and in vivo models of OS.
Main Methods:
- PD-L1 mRNA expression in OS tissues was quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
- Cell Counting Kit-8 (CCK-8) and flow cytometry were used to assess cell proliferation and apoptosis, respectively.
- In vivo studies involved treating syngeneic mice with cisplatin and anti-PD-1 antibody, alone and in combination.
Main Results:
- High PD-L1 mRNA expression was observed in osteosarcoma tissues.
- Combined anti-PD-1 antibody and cisplatin treatment significantly reduced proliferation and increased apoptosis of K7M2 cells in vitro.
- In vivo, this combination therapy markedly inhibited tumor growth without involving regulatory T cells.
Conclusions:
- Blocking the PD-1/PD-L1 axis demonstrates a positive prognostic value in enhancing cisplatin chemotherapy for osteosarcoma.
- These findings support the use of PD-1/PD-L1 blocking antibodies with cisplatin for treating refractory OS.
- This combination therapy presents a promising strategy for improving outcomes in osteosarcoma patients.
