Tumor specimens from individuals with glioblastoma multiforme (GBM) had levels of B7-H1 protein that correlated with PTEN loss, and tumor-specific T cells lysed human glioma targets expressing wild-type PTEN more effectively than those expressing mutant PTEN.
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.
Remarkably, we found that upregulation of PD-L1 by neurons in tumor-adjacent brain tissue (TABT) associated positively with GBM patient survival, whereas lack of neuronal PD-L1 expression was associated with high PD-L1 in tumors and unfavorable prognosis.
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.
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.
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.
Successful treatment with a combination of anti-VEGFR2 and anti-PD-L1 antibodies induced high endothelial venules (HEVs) in PyMT (polyoma middle T oncoprotein) breast cancer and RT2-PNET (Rip1-Tag2 pancreatic neuroendocrine tumors), but not in glioblastoma (GBM).
This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma.
In conclusion, our data proposes poly(I:C) treatment combined with PD-L1 blockade to invigorate the immune checkpoint inhibition response in glioblastoma.
Finally, we demonstrated that PD-L1 overexpression promoted while knockdown abolished GBM development and invasion in orthotopic GBM models of rodents.
PD-L1 expression correlated with the mesenchymal transcriptome profile and was anatomically localized in the perinecrotic and pseudopalisading niche of human glioblastoma specimens.
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.