Researchers have identified a subset of glioblastoma tumors using immunohistochemistry (IHC) that may be candidates for immunotherapy. The subset, classified as mesenchymal or IGS cluster 23, was identified by low expression of SOX2 and high expression of SHC1 and TCIRG1 antibodies.

To make this discovery, the researchers performed RNA sequencing, IHC, and immune-phenotyping on 124 uniformly treated glioblastoma tumor samples from patients with newly diagnosed disease. They found that the molecular subtypes had different patterns of protein expression.

Other subsets identified included The Cancer Genome Atlas (TCGA) classical subtype, identified by high expression of EGFR and low expression of PTEN. The TCGA subtype was found to overlap with the IGS cluster 18, and the proneural subtype, which was identified by frequent positive IDH1 expression and high Olig2 and Ki67 expression.

Immune-phenotyping of the mesenchymal and IGS cluster 23 tumors revealed patterns. These subtypes had a higher positive effector cell score, higher negative suppressor cell score, and lower levels of immune checkpoint molecules.


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The researchers conducted a cell-type deconvolution analysis and found that the mesenchymal and IGS cluster 23 tumors were highly enriched in M2 macrophages, resting memory CD4-positive T cells, and activated dendritic cells, “indicating that they may be ideal candidates for immunotherapy, especially with anti-M2 and/or dendritic cell vaccination,” the study authors stated.

The IHC methods applied during this evaluation, the investigators wrote, could be easily incorporated into clinical practice to identify optimal candidates for immunotherapy.

Limitations to the study included its retrospective nature and the use of formalin-fixed, paraffin-embedded specimens for the TCGA subtyping.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry and/or the medical device industry. Please see the original reference for a full list of disclosures.

Reference

Carrato C, Alameda F, Esteve-Codina A, et al. Glioblastoma TCGA mesenchymal and IGS 23 tumors are identifiable by IHC and have an immune-phenotype indicating a potential benefit from immunotherapy. Clin Can Res. 2020;26(24):6600-6609.doi:10.1158/1078-0432.CCR-20-2171.