肿瘤细胞治疗研究
英文原题：Spatial dynamics of CD39(+)CD8(+) exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer.
Spatial dynamics of CD39(+)CD8(+) exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer.
我们的研究结果表明，这一独特的CD39 + PD-1 + CD8 + T细胞亚群对ICB获益至关重要，并提示其在TLS介导的抗肿瘤免疫反应中发挥关键作用。
尽管免疫检查点阻断（ICB）治疗在食管鳞状细胞癌中取得了成功，但影响ICB疗效的关键免疫细胞群体仍不清楚。在此，对接受ICB治疗的患者肿瘤组织进行成像质谱流式分析，鉴定出一群独特的CD39 + PD-1 + CD8 + T细胞，特别是TCF1 + 亚群，即前体耗竭T（CD39 + Tpex）细胞，其与ICB获益呈正相关。CD39 + Tpex细胞主要位于间质中，而分化的CD39 + 耗竭T细胞则大量且邻近地存在于实质内。值得注意的是，CD39 + Tpex细胞集中于三级淋巴结构（TLS）内及其周围。因此，与缺乏TLS的肿瘤相比，含有TLS的肿瘤在肿瘤区域内有更多这些细胞，提示Tpex细胞从TLS向肿瘤募集。此外，在ICB治疗后，应答者中循环CD39 + Tpex细胞也增加。我们的研究结果表明，这一独特的CD39 + PD-1 + CD8 + T细胞亚群对ICB获益至关重要，并提示其在TLS介导的抗肿瘤免疫应答中发挥关键作用。
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.
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