A new antisarcoma strategy:: multisubtype heat shock protein/peptide immunotherapy combined with PD‑L1 immunological checkpoint inhibitors
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[1] Institute 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
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- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 23, Nº. 8, 2021, págs. 1688-1704
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
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 efect 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 efective 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 efectively 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
