A new antisarcoma strategy: multisubtype heat shock protein/peptide immunotherapy combined with PD-L1 immunological checkpoint inhibitors

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.

Heat Shock Proteins and HSF1 in Cancer

“…The effects of a multi-subtype HSP/peptide vaccine tested in murine osteosarcoma were potentiated by the addition of a PD-L1 inhibitor. The combination triggered elevated cytokine production, stimulated CD4+ and CD8+ T cells and mitigated lung metastasis better than each therapeutic modality alone ( 215 ). Almost all HSP-inhibitors have been administered so far on intermittent dosage schemes.…”

NIR-II Fluorescent Molecular Bottlebrush Prepared by Ring-Opening Polymerization for Programmed Cell Death Ligand-1 Checkpoint Imaging

“…Currently, the development of mAbs to block programmed death-1 receptor (PD-1)/programmed death-ligand 1 (PD-L1) has made substantial advances. The related research has been intensively and extensively reviewed. − In recent studies, immune checkpoint therapies have shown effectiveness in treating non-squamous cell lung cancer, non-small lung cancer, melanoma, Merkel cell carcinoma, head and neck squamous cell carcinoma, and hepatocellular carcinoma. , For these checkpoint therapies, the expression of PD-L1 is an important biomarker in tissue biopsies. To analyze the immune reaction to PD-1/PD-L1 immune checkpoint treatment, ex vivo biopsy with immunohistochemistry is widely used in the clinic, but it is not appropriate for dynamic monitoring and assessing the PD-L1 heterogeneity.…”