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Purpose <p>Glioblastoma is characterized by profound immune dysregulation at both intratumoral and systemic levels. Whether the peripheral immune landscape reflects tumor-related clinical and radiological features and carries prognostic relevance remains unclear. We investigated whether systemic immune cell subsets and circulating cytokines at diagnosis are associated with disease characteristics and survival in newly diagnosed glioblastoma.</p> Methods <p>Peripheral blood mononuclear cells (PBMCs) and plasma were collected preoperatively from patients treated between 2019 and 2024. Immune profiling was performed by flow cytometry, and circulating cytokines were assessed using a multiplex CD8/NK cytokine assay.</p> Results <p>Sixty-six patients with newly diagnosed IDH-wildtype glioblastoma were included. Median overall survival (OS) was 14.4 months, and median progression-free survival (PFS) was 8.5 months. Classical monocyte and myeloid-derived suppressor cell (MDSC) frequencies correlated with contrast-enhancing tumor volume. Higher classical monocyte frequencies were associated with shorter OS, whereas higher frequencies of immature natural killer (NK) cells were independently associated with longer OS. Cytotoxic cytokines inversely correlated with suppressive myeloid subsets and positively with immature NK cells, supporting a coordinated systemic immune polarization. Corticosteroid use at sampling did not significantly affect key immune subpopulations.</p> Conclusions <p>Integrated peripheral immune and cytokine profiling identifies a coordinated systemic immune axis linking tumor burden, myeloid expansion, and survival in newly diagnosed glioblastoma. Immature NK cell frequency is independently associated with improved survival, whereas classical monocytes and MDSCs reflect adverse immune polarization. These findings support the development of accessible peripheral immune biomarkers for risk stratification and translational strategies.</p>

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Prognostic relevance and cytokine correlates of peripheral immune subpopulations in newly diagnosed glioblastoma

  • 期刊论文

  • 发表日期：

    2026年3月7日

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  • Francesca Roncelli,
  • Silvia Snider,
  • Daniela Boselli,
  • Pierfrancesco De Domenico,
  • Bernhard Gentner,
  • Chiara Villa,
  • Pietro Mortini,
  • Filippo Gagliardi

摘要

Purpose

Glioblastoma is characterized by profound immune dysregulation at both intratumoral and systemic levels. Whether the peripheral immune landscape reflects tumor-related clinical and radiological features and carries prognostic relevance remains unclear. We investigated whether systemic immune cell subsets and circulating cytokines at diagnosis are associated with disease characteristics and survival in newly diagnosed glioblastoma.

Methods

Peripheral blood mononuclear cells (PBMCs) and plasma were collected preoperatively from patients treated between 2019 and 2024. Immune profiling was performed by flow cytometry, and circulating cytokines were assessed using a multiplex CD8/NK cytokine assay.

Results

Sixty-six patients with newly diagnosed IDH-wildtype glioblastoma were included. Median overall survival (OS) was 14.4 months, and median progression-free survival (PFS) was 8.5 months. Classical monocyte and myeloid-derived suppressor cell (MDSC) frequencies correlated with contrast-enhancing tumor volume. Higher classical monocyte frequencies were associated with shorter OS, whereas higher frequencies of immature natural killer (NK) cells were independently associated with longer OS. Cytotoxic cytokines inversely correlated with suppressive myeloid subsets and positively with immature NK cells, supporting a coordinated systemic immune polarization. Corticosteroid use at sampling did not significantly affect key immune subpopulations.

Conclusions

Integrated peripheral immune and cytokine profiling identifies a coordinated systemic immune axis linking tumor burden, myeloid expansion, and survival in newly diagnosed glioblastoma. Immature NK cell frequency is independently associated with improved survival, whereas classical monocytes and MDSCs reflect adverse immune polarization. These findings support the development of accessible peripheral immune biomarkers for risk stratification and translational strategies.