Malignant pleural effusion (MPE), which is a complex microenvironment that contains numerous immune and tumour signals, is common in lung cancer. Gene alterations, such as driver gene mutations, are believed to affect the components of tumour immunity in the microenvironment (TIME) of non-small-cell lung cancer. In this study, we have shown that pleural CD39 + CD8 + T cells are selectively elevated in lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFRwt) compared to those with newly diagnosed mutant EGFR (EGFRmu). Furthermore, these CD39 + CD8 + T cells are more prevalent in MPE with acquired resistance to EGFR-tyrosine kinase inhibitors (AR-EGFR-TKIs). Our analysis reveals that pleural CD39 + CD8 + T cells exhibit an exhausted phenotype while still retaining cytolytic function. Additionally, they have a higher T cell receptor (TCR) repertoire clonality compared to CD39-CD8 + T cells, which is a unique characteristic of LUAD-related MPE. Further investigation has shown that TCR-Vβ clonality tends to be more enhanced in pleural CD39 + CD8 + T cells from MPE with AR-EGFR-TKIs. In summary, we have identified a subset of CD8 + T cells expressing CD39 in MPE, which may potentially be tumour-reactive CD8 + T cells. This study provides new insights into the dynamic immune composition of the EGFRmu tumour microenvironment.

中文翻译：

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CD39 识别肺腺癌相关转移性胸腔积液中的特定 CD8 + T 细胞群

恶性胸腔积液（MPE）是一种复杂的微环境，包含大量免疫和肿瘤信号，在肺癌中很常见。基因改变，例如驱动基因突变，被认为会影响非小细胞肺癌微环境（TIME）中肿瘤免疫的组成部分。在这项研究中，我们发现，与新诊断的突变型 EGFR (EGFRmu) 患者相比，野生型表皮生长因子受体 (EGFRwt) 肺腺癌 (LUAD) 中胸膜 CD39 + CD8 + T 细胞选择性升高。此外，这些 CD39 + CD8 + T 细胞在对 EGFR 酪氨酸激酶抑制剂 (AR-EGFR-TKI) 产生耐药性的 MPE 中更为普遍。我们的分析表明，胸膜 CD39 + CD8 + T 细胞表现出耗尽的表型，同时仍保留溶细胞功能。此外，与 CD39-CD8 + T 细胞相比，它们具有更高的 T 细胞受体 (TCR) 库克隆性，这是 LUAD 相关 MPE 的独特特征。进一步的研究表明，使用 AR-EGFR-TKI 进行 MPE 的胸膜 CD39 + CD8 + T 细胞中的 TCR-Vβ 克隆性趋于增强。总之，我们在 MPE 中鉴定出了表达 CD39 的 CD8 + T 细胞子集，它们可能是肿瘤反应性 CD8 + T 细胞。这项研究为 EGFRmu 肿瘤微环境的动态免疫组成提供了新的见解。