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• W4387579013 abstract "Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8+ Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8+ T cells enforces Tpex phenotype and enhances ICB efficacy. Additionally, CD8+ Tex-SPRY1 cells contribute to proinflammatory phenotype of macrophages and functional state of B cells, which thereby promotes antitumor immunity by enhancing CD8+ T cell effector functions. Overall, our findings unravel progenitor-like CD8+ Tex-SPRY1 cells' role in effective responses to ICB for ESCC and inform mechanistic biomarkers for future individualized immunotherapy." @default.
• W4387579013 created "2023-10-13" @default.
• W4387579013 creator A5002094342 @default.
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• W4387579013 date "2023-10-01" @default.
• W4387579013 modified "2023-10-17" @default.
• W4387579013 title "Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma" @default.
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