尽管免疫检查点阻断（ICB）治疗食管鳞状细胞癌取得了成功，但影响 ICB 疗效的关键免疫细胞群仍不清楚。在这里，对接受 ICB 治疗的患者肿瘤组织进行成像质量流式细胞术，鉴定出 CD39 PD-1 CD8 T 细胞的独特细胞群，特别是 TCF1 子集、前体耗尽 T (CD39 Tpex) 细胞，其与 ICB 益处呈正相关。 CD39 Tpex 细胞主要存在于基质中，而分化的 CD39 耗尽 T 细胞则大量存在于实质内的近端。值得注意的是，CD39 Tpex 细胞集中在三级淋巴结构 (TLS) 内部和周围。因此，与缺乏 TLS 的肿瘤相比，携带 TLS 的肿瘤在肿瘤区域中具有更多的此类细胞，这表明 Tpex 细胞从 TLS 募集到肿瘤。此外，ICB 治疗后应答者中循环 CD39 Tpex 细胞也有所增加。我们的研究结果表明，这种独特的 CD39 PD-1 CD8 T 细胞亚群对于 ICB 的益处至关重要，并表明在 TLS 介导的肿瘤免疫反应中发挥着关键作用。© 2024。作者。

Despite the success of immune checkpoint blockade (ICB) therapy for esophageal squamous cell cancer, the key immune cell populations that affect ICB efficacy remain unclear. Here, imaging mass cytometry of tumor tissues from ICB-treated patients identifies a distinct cell population of CD39+PD-1+CD8+ T cells, specifically the TCF1+ subset, precursor exhausted T (CD39+ Tpex) cells, which positively correlate with ICB benefit. CD39+ Tpex cells are predominantly in the stroma, while differentiated CD39+ exhausted T cells are abundantly and proximally within the parenchyma. Notably, CD39+ Tpex cells are concentrated within and around tertiary lymphoid structure (TLS). Accordingly, tumors harboring TLSs have more of these cells in tumor areas than tumors lacking TLSs, suggesting Tpex cell recruitment from TLSs to tumors. In addition, circulating CD39+ Tpex cells are also increased in responders following ICB therapy. Our findings show that this unique subpopulation of CD39+PD-1+CD8+ T cells is crucial for ICB benefit, and suggest a key role in TLS-mediated immune responses against tumors.© 2024. The Author(s).