Glioblastoma TCGA mesenchymal and IGS 23 tumors are identifiable by immunohistochemistry and have an immune-phenotype indicating potential benefit from immunotherapy
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- dc.contributor.author Carrato, Cristina
- dc.contributor.author Alameda Quitllet, Francisco
- dc.contributor.author Esteve-Codina, Anna
- dc.contributor.author Arpí Llucià, Oriol
- dc.contributor.author Gut, Marta
- dc.contributor.author Menéndez, Silvia
- dc.contributor.author Balana, Carmen
- dc.date.accessioned 2020-10-08T06:16:08Z
- dc.date.issued 2020
- dc.description.abstract Purpose: Molecular subtype classifications in glioblastoma may detect therapy sensitivities. Immunohistochemistry would potentially allow the identification of molecular subtypes in routine clinical practice. Experimental design: Paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed glioblastoma patients were submitted to RNA-Sequencing, immunohistochemistry, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities. Results: We detected high molecular and immunohistochemical overlapping of the TCGA mesenchymal subtype with IGS cluster 23 and of the TCGA classical subtype with IGS cluster 18. Immunohistochemical patterns, gene fusion profiles, and immune-phenotypes varied across subtypes. Immunohistochemistry revealed that the TCGA classical subtype was identified by high expression of EGFR and low expression of PTEN, while the mesenchymal subtype was identified by low expression of SOX2 and high expression of two antibodies, SHC1 and TCIRG1, selected based on RNA differential transcriptomic expression. The proneural subtype was identified by frequent positive IDH1 expression and high Olig2 and Ki67 expression. Immune-phenotyping showed that mesenchymal and IGS 23 tumors exhibited a higher positive effector cell score, a higher negative suppressor cell score, and lower levels of immune checkpoint molecules. The cell-type deconvolution analysis revealed that these tumors are highly enriched in M2 macrophages, resting memory CD4+ T cells, and activated dendritic cells, indicating that they may be ideal candidates for immunotherapy, especially with anti-M2 and/or dendritic cell vaccination. Conclusions: There is a subset of tumors, frequently classified as mesenchymal or IGS cluster 23, that may be identified with immunohistochemistry and could well be optimal candidates to immunotherapy.
- dc.format.mimetype application/pdf
- dc.identifier.citation Carrato C, Alameda F, Esteve-Codina A, Pineda E, Arpí O, Martinez Garcia M et al. Glioblastoma TCGA mesenchymal and IGS 23 tumors are identifiable by immunohistochemistry and have an immune-phenotype indicating potential benefit from immunotherapy. Clin Cancer Res. 2020;26(24):6600-9. DOI: 10.1158/1078-0432.CCR-20-2171
- dc.identifier.doi http://dx.doi.org/10.1158/1078-0432.CCR-20-2171
- dc.identifier.issn 1078-0432
- dc.identifier.uri http://hdl.handle.net/10230/45425
- dc.language.iso eng
- dc.publisher American Association for Cancer Research (AACR)
- dc.relation.ispartof Clin Cancer Res. 2020;26(24):6600-9
- dc.rights © American Association for Cancer Research (AACR) http://dx.doi.org/10.1158/1078-0432.CCR-20-2171
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.title Glioblastoma TCGA mesenchymal and IGS 23 tumors are identifiable by immunohistochemistry and have an immune-phenotype indicating potential benefit from immunotherapy
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion