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Identification of Molecularly Targeted Therapy-Induced Immunopeptidome in Diffuse Midline Glioma (DMG)

ABSTRACT: We used MHC-I immunopeptidomics to study how MTX-241F, a selective EGFR/PI3K inhibitor, alters antigen presentation in diffuse midline glioma (H3K27M) and glioblastoma xenografts. MHC-I–bound peptides from vehicle- and drug-treated tumors were profiled by LC–MS/MS to identify tumor- and treatment-specific peptides, including candidate brain-enriched biomarkers and immunotherapy targets.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Permanent Cell Line Cell

DISEASE(S): Glioblastoma,Diffuse Midline Glioma

SUBMITTER: Habeebah Owolabi

LAB HEAD: Stefanie Galban

PROVIDER: PXD070941 | Pride | 2026-02-10

REPOSITORIES: Pride

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			Action	DRS
	DIPG_treated.raw	Raw
	DIPG_treated_M1_42.raw	Raw
	DIPG_vehicle.raw	Raw
	DIPG_vehicle_M1_42.raw	Raw
	Fragpipe_Results.csv	Csv

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Publications

Identification of molecularly targeted therapy-induced immunopeptidome in diffuse midline glioma (DMG).

Khairkhah Niloofar N Owolabi Habeebah H Namvar Ali A Ibrahim Mostafa M H MMH Nyayapathy Seeta S Jones Richard R Rumble Julie M JM Whitehead Christopher E CE Sebolt-Leopold Judith S JS Everest-Dass Arun A Galban Stefanie S

Neoplasia (New York, N.Y.) 20260204

<h4>Introduction</h4>Diffuse midline glioma (DMG) with the H3K27M mutation remains one of the most treatment-resistant pediatric brain tumors, in part due to limited antigen presentation and immune visibility. Exploring how glioma biology and therapeutic interventions influence immune recognition offers new opportunities to identify tumor-specific immune targets.<h4>Materials and methods</h4>We performed immunopeptidomics on human cell line derived tumor tissue for DMG and glioblastoma (GBM) and ...[more]

PMID: 41643293

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Project description:Mutations in the gene encoding histone H3, p.K28M(K27M) and p.G35R/V(G34R/V), are the major driver gene mutations in gliomas. H3 p.K28M(K27M) mutations are frequently found in gliomas arising in midline structures, so called H3K27M-diffuse midline glioma (DMG), while H3 p.G35R/V(G34R/V) mutations are frequently found in pediatric hemispheric gliomas, so called H3G34R/V-diffuse hemispheric glioma (DHG). In contrast, hemispheric glioma with H3 p.K28M(K27M) mutation, known as H3K27M-DHG, is a rare entity and its clinical and molecular characteristics remain to be fully elucidated. We describe a 41-year-old female patient with the right parietal lobe tumor. Following a gross total resection, the pathology showed a high-grade astrocytoma. Sanger sequencing revealed an H3K27M mutation and an IDH1/2-wildtype, leading to the integrated diagnosis of H3K27M-DHG. She underwent chemoradiotherapy with temozolomide and suffered recurrences twice until her death 55 months after the initial diagnosis. The deoxyribonucleic acid methylation profiling classified the tumor as DMG, H3K27-altered, suggesting that it molecularly belonged to the variant of DMG despite a non-median location. Next-generation sequencing on the recurrent tumor detected fibroblast growth factor receptor (FGFR)1 mutation, a favorable prognostic factor in H3K27M-DMG. A relatively prolonged survival of our patient suggests that FGFR1 mutations may also contribute to a better prognosis in H3K27M-DHG.

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