<b>Conclusion:</b> GDF15 might be a novel regulator of PD-L1 expression in GBMs; targeting GDF15/PD-L1 pathway might be a promising therapeutic approach for GBM patients.
PDL-1 partially affected the IFN-gamma production of antigen-specific T cells in response to GBM primary cell lines, and IDO inhibited lymphocyte proliferation induced by lectins.
PD-L1 expression correlated with the mesenchymal transcriptome profile and was anatomically localized in the perinecrotic and pseudopalisading niche of human glioblastoma specimens.
A multivariate proportional hazards model revealed MGMT methylation, Karnofsky performance status, and PD-L1 expression as the primary independent predictors of survival.<b>Conclusions:</b> Vaccination with autologous tumor-derived heat shock proteins may improve survival for GBM patients when combined with standard therapy and warrants further study.
A Radiosensitivity Gene Signature and PD-L1 Status Predict Clinical Outcome of Patients with Glioblastoma Multiforme in The Cancer Genome Atlas Dataset.
Correlation between lower balance of Th2 helper T-cells and expression of PD-L1/PD-1 axis genes enables prognostic prediction in patients with glioblastoma.
Finally, we demonstrated that PD-L1 overexpression promoted while knockdown abolished GBM development and invasion in orthotopic GBM models of rodents.
Histopathologic analyses resulted in a diagnosis of de novo GBM that was <i>BRAF</i> wild type and negative forprogrammed death-ligand 1 protein expression.
Importantly, pevonedistat attenuates T cell killing through PD-L1 induction, and blockade of PD-L1 restores the sensitivity of pevonedistat-treated glioblastoma cancer cells to T cell killing.
In conclusion, our data proposes poly(I:C) treatment combined with PD-L1 blockade to invigorate the immune checkpoint inhibition response in glioblastoma.
In summary, the ongoing clinical studies evaluating the activity of PD-1/PD-L1 inhibitors in glioblastoma need to be complemented with well designed and stringently executed studies to understand the influence of PD-1/PD-L1 expression on therapy response or failure and to develop robust means of PD-L1 assessment for meaningful biomarker development.
In this review, we describe the immunosuppressive molecular characteristics of the tumour microenvironment (TME), candidate biomarkers of PD-1/PD-L1 checkpoint blockades, ongoing clinical trials and challenges of PD-1/PD-L1 checkpoint blockades in glioblastoma.
In this study, we developed a cyclic peptide iRGD (CCRGDKGPDC)-conjugated solid lipid nanoparticle (SLN) to deliver small interfering RNAs (siRNAs) against both epidermal growth factor receptor (EGFR) and PD-L1 for combined targeted and immunotherapy against glioblastoma, the most aggressive type of brain tumors.
Moreover, lncRNA RP11-571M6.8 was detected to be highly associated with immunotherapeutic targets (PD-1, PD-L1, and CTLA-4) and regulatory T cell infiltration level and their markers (IL2RA and FCGR2B) in glioblastoma multiforme, highlighting its immunosuppressive function.
Mutations of PTEN, tumor protein 53, BRAF, IDH1, and epidermal growth factor receptor or MGMT-Me did not associate with increased intratumoral expression of either PD-1+ TIL or PD-L1 in glioblastoma multiforme even before false discovery rate correction for multiple comparison.