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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Frontiers Media S.A.
2025-01-01
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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. |
format | Article |
id | doaj-art-46551f36a2c54cd096932317e2cc2567 |
institution | Kabale University |
issn | 1664-3224 |
language | English |
publishDate | 2025-01-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
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 |
work_keys_str_mv | AT yifushu disulfidptosisasakeyregulatorofglioblastomaprogressionandimmunecellimpairment AT jingli disulfidptosisasakeyregulatorofglioblastomaprogressionandimmunecellimpairment |