Glioblastoma TCGA Mesenchymal and IGS 23 Tumors are Identifiable by IHC and have an Immune-phenotype Indicating a Potential Benefit from Immunotherapy
Por:
Carrato, C, Alameda, F, Esteve-Codina, A, Pineda, E, Arpi, O, Martinez-Garcia, M, Mallo, M, Gut, M, Lopez-Martos, R, Del Barco, S, Ribalta, T, Capellades, J, Puig, J, Gallego, O, Mesia, C, Munoz-Marmol, AM, Archilla, I, Arumi, M, Blanc, JM, Bellosillo, B, Menendez, S, Esteve, A, Bague, S, Hernandez, A, Craven-Bartle, J, Fuentes, R, Vidal, N, Aldecoa, I, de la Iglesia, N and Balana, C
Publicada:
15 dic 2020
Ahead of Print:
30 sep 2020
Resumen:
Purpose: Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC would potentially allow the identification of molecular subtypes in routine clinical practice.
Experimental Design: Formalin-fixed, paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed patients with glioblastoma were submitted to RNA sequencing, IHC, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities.
Results: We detected high molecular and IHC overlapping of the The Cancer Genome Atlas (TCGA) mesenchymal subtype with instrinsic glioma subtypes (IGS) cluster 23 and of the TCGA classical subtype with IGS duster 18. IHC patterns, gene fusion profiles, and immune-phenotypes varied across subtypes. IHC revealed that the TCGA dassical 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 TCIRGI, selected on the basis of 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 IHC and could well be optimal candidates for immunotherapy.
Filiaciones:
:
Hosp Badalona Germans Trias & Pujol, Pathol Dept, Badalona, Spain
Alameda, F:
Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Pathol Dept, Neuropathol Unit, Barcelona, Spain
Esteve-Codina, A:
Ctr Genom Regulat, Barcelona Inst Sci & Technol, CNAG CRG, Barcelona, Spain
Pineda, E:
Hosp Clin Barcelona, August Pi & Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Med Oncol, Barcelona, Spain
Arpi, O:
Inst Hosp del Mar Invest Med IMIM, Canc Res Program, Barcelona, Spain
Martinez-Garcia, M:
Hosp del Mar, Med Oncol, Barcelona, Spain
:
Inst Recerca Leucemia Josep Carreras, Badalona, Spain
Gut, M:
Univ Pompeu Fabra UPF, Ctr Genom Regulat CRG, Barcelona Inst Sci & Technol, CNAG CRG, Barcelona, Spain
Lopez-Martos, R:
Hosp Badalona Germans Trias & Pujol, Pathol Dept, Badalona, Spain
Del Barco, S:
Hosp Josep Trueta, Inst Catala Oncol ICO Girona, Med Oncol, Girona, Spain
Ribalta, T:
Hosp Clin Barcelona, Pathol Dept Neuropathol, Barcelona, Spain
Capellades, J:
Hosp del Mar, Radiol Dept, Barcelona, Spain
Puig, J:
Hosp Josep Trueta, Inst Diagnost Imatge, Radiol Dept, Girona, Spain
Gallego, O:
Hosp Santa Creu & Sant Pau, Med Oncol, Barcelona, Spain
Mesia, C:
Inst Catala Oncol ICO, Inst Invest Bellvitge IDIBELL, Neurooncol Unit, Barcelona, Spain
Inst Catala Oncol ICO, Inst Invest Bellvitge IDIBELL, Med Oncol Dept, Barcelona, Spain
:
Hosp Badalona Germans Trias & Pujol, Pathol Dept, Badalona, Spain
Archilla, I:
Hosp Clin Barcelona, Pathol Dept Neuropathol, Barcelona, Spain
Arumi, M:
Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Pathol Dept, Neuropathol Unit, Barcelona, Spain
Blanc, JM:
Hosp Badalona Germans Trias & Pujol, Pathol Dept, Badalona, Spain
Bellosillo, B:
Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Pathol Dept, Neuropathol Unit, Barcelona, Spain
Menendez, S:
Inst Hosp del Mar Invest Med IMIM, Canc Res Program, Barcelona, Spain
:
Inst Catala Oncol ICO Badalona, Inst Invest Germans Trias & Pujol IGTP, Badalona Appl Res Grp Oncol B ARGO Grp, Ctra Canyet S-N, Badalona 08916, Spain
Bague, S:
Hosp Santa Creu & Sant Pau, Pathol Dept, Barcelona, Spain
:
Inst Catala Oncol ICO Badalona, Inst Invest Germans Trias & Pujol IGTP, Badalona Appl Res Grp Oncol B ARGO Grp, Ctra Canyet S-N, Badalona 08916, Spain
Craven-Bartle, J:
Hosp Santa Creu & Sant Pau, Radiat Therapy Dept, Barcelona, Spain
Fuentes, R:
Inst Catala Oncol ICO, Radiat Therapy Dept, Girona, Spain
Vidal, N:
Hosp Bellvitge Princeps Espanya, Pathol Dept, Bellvitge, Spain
Aldecoa, I:
Hosp Clin Barcelona, Pathol Dept Neuropathol, Barcelona, Spain
Biobanc Hosp Clin IDIBAPS, Neurol Tissue Bank, Barcelona, Spain
de la Iglesia, N:
August Pi & Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Glioma & Neural Stem Cell Grp, Barcelona, Spain
:
Inst Catala Oncol ICO Badalona, Inst Invest Germans Trias & Pujol IGTP, Badalona Appl Res Grp Oncol B ARGO Grp, Ctra Canyet S-N, Badalona 08916, Spain
Green Accepted
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