On this basis, findings of the current study demonstrates that the pharmacological or genetic abrogation of HDAC6 in osteosarcoma cell lines down-regulates the expression of program death receptor ligand-1 (PD-L1), an important co-stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD-1 in T cells.
We provide a description of the landscape of programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1) and relevant immune markers in serial samples from 15 osteosarcoma patients.
Our findings may contribute to the development of precise treatments for osteosarcoma based on the expression profile of PD‑L1 in patients with this disease.
When administered in tandem, Nb6 and <sup>124</sup>I-anti-hPD-L1 Nb6 may provide a novel strategy to clinically screen patients for hPD-L1 to identify those who would benefit from immunotherapy of malignant tumors such as osteosarcoma.
These findings provide the basis for establishing CXCR4 antagonist and PD-1/PD-L1 inhibitors co-administration as a novel therapeutic regimen for patients with osteosarcoma and hold great promise for improving the therapeutic effect of osteosarcoma.
In short, the combination of conventional chemotherapy and an anti-PD-L1 antibody might be an effective option for osteosarcoma treatment, as anti-PD-L1 antibody can reverse the immunosuppression induced by chemotherapy.
Osteosarcoma cells are able to affect the balance between M1 and M2 macrophage subtypes and so could control the T-lymphocyte responses via the PD-1/PDL-1 system.
Meanwhile, we also confirmed the down-regulation of PD-L1 in osteosarcoma in response to PDT and 3-MA treatment, which significantly inhibited tumor growth in a model of tumor metastasis.
We systematically detected the expression patterns of PD-L1, PD-L2, and PD-1 in musculoskeletal tumors for the first time and demonstrated the prognostic roles and underlying mechanisms of PD-1 axis in osteosarcoma.
To investigate the clinical significance of vascular endothelial growth factor receptor-2 (VEGFR2) and programmed death ligand-1 (PD-L1) in osteosarcoma, we analyzes their expression levels in 93 osteosarcoma specimens by immunohistochemistry.
Collectively, our findings indicate that miR-140 exerts anti-OS efficacy by targeting immune checkpoint molecule PD-L1 and can be developed as a novel immunotherapeutic agent for the treatment of OS.
In this study, we asked if the targetable immune checkpoints <i>CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3)</i> and <i>IDO1</i> are impacted by copy number alterations in osteosarcoma.
Pooled results showed that PD-L1/PD-1 overexpression was significantly associated with metastasis (RR = 1.54, 95% CI: 1.12-2.11, p = 0.008) in osteosarcoma.
As a result, this combination treatment strategy significantly prolonged survival of osteosarcoma bearing mice, suggesting that L-arginine supplementation in combination with α-PD-L1 antibody may be a promising method for osteosarcoma patients.
These results suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of osteosarcoma.
Pooled hazard ratios indicated that the association of PD-L1 expression with overall survival in bone sarcoma (osteosarcoma and chondrosarcoma) patients was statistically significant (1.987, 95% CI: 1.224-3.224, <i>p</i> = 0.005), as was its association with event-free survival in bone and soft-tissue sarcoma patients (3.868, 95% CI: 2.298-6.511, <i>p</i> = 0.000).
Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy.
Quantitative real-time RT-PCR for PDL1 was optimized in 18 cell lines, of which 5 were osteosarcoma derived. qRT-PCR results were validated via flow cytometry and immunohistochemistry (IHC) in select cell lines.