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

BACKGROUND: Glioblastoma, associated with poor prognosis and impaired immune function, shows potential interactions between newly identified disulfidptosis mechanisms and T cell exhaustion, yet these remain understudied. METHODS: Key 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. RESULTS: Eleven 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. CONCLUSIONS: Disulfidptosis-Tex genes are pivotal in glioblastoma progression and immune interactions, offering new avenues for improving anti-glioblastoma therapies through modulation of T cell exhaustion.