通过单细胞分析在晚期肺癌患者的恶性胸腔积液中鉴定出候选肿瘤特异性 CD8 T 细胞亚群。
Candidate tumor-specific CD8+ T cell subsets identified in the malignant pleural effusion of advanced lung cancer patients by single-cell analysis.
发表日期：2024
作者：
Yusuke Sugita, Daisuke Muraoka, Ayako Demachi-Okamura, Hiroyasu Komuro, Katsuhiro Masago, Eiichi Sasaki, Yasunori Fukushima, Takuya Matsui, Shuichi Shinohara, Yusuke Takahashi, Reina Nishida, Chieko Takashima, Teppei Yamaguchi, Yoshitsugu Horio, Kana Hashimoto, Ichidai Tanaka, Hiroshi Hamana, Hiroyuki Kishi, Daiki Miura, Yuki Tanaka, Kousuke Onoue, Kazuhide Onoguchi, Yoshiko Yamashita, Richard Stratford, Trevor Clancy, Rui Yamaguchi, Hiroaki Kuroda, Hironori Ishibashi, Kenichi Okubo, Hirokazu Matsushita
来源：
OncoImmunology
摘要：
从恶性胸腔积液 (MPE) 中分离肿瘤特异性 T 细胞及其抗原受体 (TCR) 可能有助于为晚期肺癌患者开发 TCR 转导的过继性细胞免疫治疗产品。然而，MPE 中肿瘤特异性 T 细胞的特征和标记物在很大程度上尚不明确。为此，为了确定 CD8 T 细胞的表型和抗原特异性，我们对三名晚期肺癌患者的样本进行了单细胞 RNA 和 TCR 测序。对总共 4,983 个 CD8 T 细胞进行降维，揭示了 10 个簇，包括幼稚、记忆和耗尽表型。我们特别关注耗尽的 T 细胞簇，并测试了它们对自体癌细胞系预测的新抗原的 TCR 反应性。从其中一名患者身上鉴定出四种针对相同新抗原的不同 TCR 和一种针对自体细胞系的孤儿 TCR。肿瘤特异性 T 细胞相对于其他 T 细胞的差异基因表达分析确定了 CXCL13，作为肿瘤特异性 T 细胞表达的候选基因。除了表达CXCL13外，肿瘤特异性T细胞在共表达PDCD1(PD-1)/TNFRSF9(4-1BB)的T细胞中也存在较高比例。此外，对患有 MPE 的晚期肺癌患者进行流式细胞术分析表明，在 57 名腺癌患者中，PD-1/4-1BB 高表达的患者预后较好 (p = .039)。这些数据表明，PD-1/4-1BB 共表达可能会识别 MPE 中的肿瘤特异性 CD8 T 细胞，这与患者的预后相关。 （233 字）。© 2024 作者。由泰勒授权出版
Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8+ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8+ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13, as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13, tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1(PD-1)/TNFRSF9(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (p = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8+ T cells in MPE, which are associated with patients' prognosis. (233 words).© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.