A new antisarcoma strategy: multisubtype heat shock protein/peptide immunotherapy combined with PD-L1 immunological
1Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma War Injuries, PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
Abstract:
Osteosarcoma, a common malignant tumor in orthopedics, often has a very poor prognosis after lung metastasis. Immunotherapy has not achieved much progress in the treatment because of the characteristics of solid tumors and immune environment of osteosarcoma. The tumor environment is rather essential for sarcoma treatment. Our previous study demonstrated that heat shock proteins could be used as antitumor vaccines by carrying tumor antigen peptides, and we hypothesize that an anti-osteosarcoma effect may be increased with an immune check point inhibitor (PD-L1 inhibitor) as a combination treatment strategy. The present study prepared a multisubtype mixed heat shock protein osteosarcoma vaccine (mHSP/peptide vaccine) and concluded that the mHSP/peptide vaccine was more effective than a single subtype heat shock protein, like Grp94. Therefore, we used the mHSP/peptide vaccine in combination with a PD-L1 inhibitor to treat osteosarcoma, and the deterioration of osteosarcoma was effectively hampered. The mechanism of combined therapy was investigated, and AKT expression participates with sarcoma lung metastasis. This study proposed an antisarcoma strategy via stimulation of the immune system as a further alternative approach for sarcoma treatment and elucidated the mechanism of combined therapy.
Insights
A novel multisubunit heat shock protein (HSP)/peptide vaccine combined with a PD-L1 inhibitor effectively treated osteosarcoma by hampering tumor progression. This immunotherapy strategy also elucidated the role of AKT in sarcoma lung metastasis.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Osteosarcoma presents a poor prognosis, especially after lung metastasis, with limited immunotherapy success due to its tumor microenvironment.
- Heat shock proteins (HSPs) show potential as antitumor vaccines by presenting tumor antigens.
- Combining HSP-based vaccines with immune checkpoint inhibitors may enhance anti-osteosarcoma efficacy.
Purpose of the Study:
- To evaluate the efficacy of a multisubtype mixed HSP/peptide vaccine combined with a PD-L1 inhibitor for osteosarcoma treatment.
- To investigate the underlying mechanisms of this combination therapy, including the role of AKT in metastasis.
Main Methods:
- Preparation of a multisubtype mixed heat shock protein osteosarcoma vaccine (mHSP/peptide vaccine).
- Combination treatment of osteosarcoma using the mHSP/peptide vaccine and a PD-L1 inhibitor.
- Investigation of the mechanism of action, focusing on AKT expression and lung metastasis.
Main Results:
- The mHSP/peptide vaccine demonstrated superior efficacy compared to single-subtype HSPs.
- The combination therapy effectively inhibited osteosarcoma progression.
- AKT expression was identified as a factor involved in sarcoma lung metastasis.
Conclusions:
- The mHSP/peptide vaccine combined with PD-L1 inhibition offers a promising immunotherapy strategy for osteosarcoma.
- This approach effectively hampers tumor deterioration and provides insights into the mechanism involving AKT.
- Stimulating the immune system presents a viable alternative for sarcoma treatment.
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