Genetics and immunotherapy: using the genetic landscape of gliomas to inform management strategies

Abstract

Recent work in genetics has identified essential driver mutations in gliomas and has profoundly changed our understanding of tumorigenesis. New insights into the molecular basis of glioma has informed the development of therapies demonstrating considerable potential, including immunotherapeutic approaches such as peptide and dendritic cell vaccines against EGFRvIII. However, the selective targeting of one component of a dysregulated pathway may be inadequate for a durable clinical response, given the intratumoral heterogeneity of glioblastoma (GBM) and hypermutated profiles displayed by tumor recurrences. Immune checkpoint blockade with anti-cytotoxic T lymphocyte antigen-4 (CTLA) and anti-programmed cell death 1 (PD-1) have demonstrated encouraging results in clinical trials with other solid tumors, and recent data suggest that this type of therapy may be particularly useful for tumors with high mutational burdens. Although the survival for patients with GBM has remains grim, the use of immunotherapy may finally change patient outcomes.

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

“…Gliomas treated with DC vaccination ± murine anti–PD-1 monoclonal antibody blockade or a colony-stimulating factor 1 receptor inhibitor (PLX3397) had prolonged survival in vivo [ 74 ]. Previous studies indicate that combination therapy with immune checkpoint blockade is effective for the treatment of malignant tumors, including GBM [ 75 , 76 ].…”

Improved Prognostic Prediction of Glioblastoma using a PAS Detected from Single-cell RNA-seq

“…The mutational landscape indicated that both groups had different mutation events, and the low PAS score group was found to have an increased frequency of mutation events (Figures 5B and 5C). In addition, patients with higher mutations might have an increased number of neoantigens that will increase the sensitivity of patients to chemotherapy, immunotherapy and targeted molecular therapy [25][26][27]. Thus, these observations might provide a key reason to account for why low PAS score patients had improved prognostic outcomes.…”

Early candidate biomarkers found from urine of astrocytoma rat before changes in MRI

“…Proteins were extracted as follows [16]: (1) For each urine sample, some proteins were separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), while some proteins were digested by trypsin (Trypsin Gold, Mass Spec Grade, Promega, Fitchburg, WI, USA) in 10-kD filter units (Pall, Port Washington, NY, USA) [17]. UA (8 M urea in 0.1 M Tris-HCl, pH 8.5) was added to wash the proteins at 14000×g for 20 min at 18°C.…”