Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment

BackgroundGlioblastoma, associated with poor prognosis and impaired immune function, shows potential interactions between newly identified disulfidptosis mechanisms and T cell exhaustion, yet these remain understudied.MethodsKey genes were identified using Lasso regression, followed by multivariate...

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Main Authors: Yifu Shu, Jing Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526296/full
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author Yifu Shu
Jing Li
author_facet Yifu Shu
Jing Li
author_sort Yifu Shu
collection DOAJ
description BackgroundGlioblastoma, associated with poor prognosis and impaired immune function, shows potential interactions between newly identified disulfidptosis mechanisms and T cell exhaustion, yet these remain understudied.MethodsKey genes were identified using Lasso regression, followed by multivariate analysis to develop a prognostic model. Single-cell pseudotemporal analysis explored disulfidptosis T-cell exhaustion (Tex) signaling in cell differentiation. Immune infiltration was assessed via ssGSEA, while transwell assays and immunofluorescence examined the effects of disulfidptosis-Tex genes on glioma cell behavior and immune response.ResultsEleven disulfidptosis-Tex genes were found critical for glioblastoma survival outcomes. This gene set underpinned a model predicting patient prognosis. Single-cell analysis showed high disulfidptosis-Tex activity in endothelial cells. Memory T cell populations were linked to these genes. SMC4 inhibition reduced LN299 cell migration and increased chemotherapy sensitivity, decreasing CD4 and CD8 T cell activation.ConclusionsDisulfidptosis-Tex genes are pivotal in glioblastoma progression and immune interactions, offering new avenues for improving anti-glioblastoma therapies through modulation of T cell exhaustion.
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spelling doaj-art-46551f36a2c54cd096932317e2cc25672025-01-30T06:22:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15262961526296Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairmentYifu ShuJing LiBackgroundGlioblastoma, associated with poor prognosis and impaired immune function, shows potential interactions between newly identified disulfidptosis mechanisms and T cell exhaustion, yet these remain understudied.MethodsKey genes were identified using Lasso regression, followed by multivariate analysis to develop a prognostic model. Single-cell pseudotemporal analysis explored disulfidptosis T-cell exhaustion (Tex) signaling in cell differentiation. Immune infiltration was assessed via ssGSEA, while transwell assays and immunofluorescence examined the effects of disulfidptosis-Tex genes on glioma cell behavior and immune response.ResultsEleven disulfidptosis-Tex genes were found critical for glioblastoma survival outcomes. This gene set underpinned a model predicting patient prognosis. Single-cell analysis showed high disulfidptosis-Tex activity in endothelial cells. Memory T cell populations were linked to these genes. SMC4 inhibition reduced LN299 cell migration and increased chemotherapy sensitivity, decreasing CD4 and CD8 T cell activation.ConclusionsDisulfidptosis-Tex genes are pivotal in glioblastoma progression and immune interactions, offering new avenues for improving anti-glioblastoma therapies through modulation of T cell exhaustion.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526296/fullglioblastomadisulfidptosisPD-L1t cell exhaustionmulti-omics
spellingShingle Yifu Shu
Jing Li
Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment
Frontiers in Immunology
glioblastoma
disulfidptosis
PD-L1
t cell exhaustion
multi-omics
title Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment
title_full Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment
title_fullStr Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment
title_full_unstemmed Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment
title_short Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment
title_sort disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment
topic glioblastoma
disulfidptosis
PD-L1
t cell exhaustion
multi-omics
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526296/full
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AT jingli disulfidptosisasakeyregulatorofglioblastomaprogressionandimmunecellimpairment