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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Bibliographic Details
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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Summary: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.
ISSN:1664-3224