Immune Profiling Study Offers Potential New Patient-Stratification Tools in Glioblastoma

A new study based on immune profiling of immuno-oncology–related genes suggests a number of potential biomarkers that could help clinicians better predict the prognosis of patients with glioblastoma (GBM).

The study, published in Therapeutic Advances in Medical Oncology, shows that there are important differences between isocitrate dehydrogenase (IDH) wild-type (IDHwt) and IDH mutant (IDHmut) tumors.

GBM is the most common primary brain cancer in adults, and it is also one of the deadliest, explained the authors.

“The dismal prognosis of GBM is partly due to tumor heterogeneity and the multiplicity of altered oncogenic pathways in tumor cells,” they said.

Although GBM has been studied extensively, developments in the research have not yet led to significant improvements in patient prognosis. Still, the investigators said recent advances in scientists’ understanding of the tumor microenvironment and the immunological factors involved in tumor development and growth have fostered hope that immunotherapy may have an important role to play in the future of GBM treatment.

They sought to better understand the GBM immune microenvironment to see whether they could find insights with therapeutic or prognostic importance. The investigators obtained samples from 99 patients with IDHwt GBM and grade 4 astrocytoma IDHmut, and evaluated the expression profiles of 730 immune-oncology­–related genes using NanoString Technology Inc.’s Pan-Cancer Immune Profiling Panel. All of the patients from whom the samples were collected were treated with standard-of-care therapies.

The investigators looked at several factors, including differences in gene expression profiles, immune pathways, and cell-type scores, and then compared those findings to patient outcomes.

The analysis identified 88 upregulated and 9 downregulated genes in IDHwt GBM compared with IDHmut tumors. They also found higher immunological function and higher macrophage scores in IDHwt GBM vs IDHmut tumors.

When the investigators looked at patients with IDHwt GBM based on survival outcomes, they found 24 genes were upregulated in the cohort of patients with a shorter survival period (median overall survival [OS] of 7.95 months) compared with those who had a longer survival (median OS 42.94 months). Those short-term–survival patients also had an overexpression of CD274 programmed death-ligand 1 immune checkpoint mRNA, as well as upregulated immune pathways, CD45, cytotoxic cells, and macrophage scores.

Furthermore, the investigators said they identified a 12-gene signature that could be used to stratify patients into 2 prognostic groups: high risk and low risk.

The authors noted several limitations to their study. They only evaluated gene expression levels of a limited number of genes and they had a small sample size when assessing differences between the short- and long-term survival groups within the IDHwt GBM patient cohort.

Still, they noted that 18 of the 24 genes they identified as differentially expressed have also been linked with GBM survival in the Cancer Genome Atlas database, which theysaid suggests their results are consistent and important.

“Our findings identify several specific immune-related factors which may be associated with a more aggressive phenotype in GBM and provide promising and new unexplored targets for therapy,” they wrote.

Reference

Moreno DA, da Silva LS, Gomes I, et al. Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients' survival. Ther Adv Med Oncol. Published online December 21, 2022. doi:10.1177/17588359221127678