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A mitoxyperilysis-derived spatial signature predicts immune exclusion and survival in oral squamous cell carcinoma

· 2026-09-09 · 原文

DOI:10.64898/2026.09.04.26362241v1?rss=1

Immune checkpoint blockade offers limited clinical benefit to patients with oral squamous cell carcinoma (OSCC) harboring immune-excluded microenvironments. The spatial mechanisms maintaining this stromal barricade remain unresolved. Analyzing single-cell and spatial transcriptomics across multiple cohorts, we identified a localized immunosuppressive network driven by mitoxyperilysis, which is a mitochondria-dependent lytic cell death process. Quantitative spatial mapping revealed that ISG+ PMN-MDSCs and GZMB+ pDCs accumulate at the tumor invasive margin, where they establish a physical and metabolic barrier restricting cytotoxic T-cell infiltration. Computational network ablation confirmed that both subsets are required to maintain this exclusion. We then derived a 5-gene prognostic signa

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1. 人话版

Immune checkpoint blockade offers limited clinical benefit to patients with oral squamous cell carcinoma (OSCC) harboring immune-excluded microenvironments.

The spatial mechanisms maintaining this stromal barricade remain unresolved.

2. 领域脉络

Analyzing single-cell and spatial transcriptomics across multiple cohorts, we identified a localized immunosuppressive network driven by mitoxyperilysis, which is a mitochondria-dependent lytic cell death process.

3. 机制拆解

Quantitative spatial mapping revealed that ISG+ PMN-MDSCs and GZMB+ pDCs accumulate at the tumor invasive margin, where they establish a physical and metabolic barrier restricting cytotoxic T-cell infiltration.

Computational network ablation confirmed that both subsets are required to maintain this exclusion.

4. 证据与数字

We then derived a 5-gene prognostic signa

5. 反例与边界

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6. 跨领域连接与意外收获

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7. 可复用方法

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8. 术语表

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