IGH repertoire analysis at scale: deciphering the complexity of B cell infiltration and migration in esophageal squamous cell carcinoma
IGH repertoire analysis at scale: deciphering the complexity of B cell infiltration and migration in esophageal squamous cell carcinoma
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DOI：
10.1038/s41417-023-00689-w
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发表时间：
2023-11-20
影响因子：
6.4
通讯作者：
Zhang，Weimin
中科院分区：
文献类型：
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作者：
Wang，Longlong;Zhou，Yong;Zhang，Weimin
肿瘤浸润 B 谱系细胞已成为各种癌症预后和免疫治疗反应的预测因子。然而，对其渗透和迁移模式的了解有限，阻碍了对其抗肿瘤功能的理解。在这里，我们检查了从 107 名食管鳞状细胞癌 (ESCC) 患者获得的 496 个多区域肿瘤、107 个正常组织和 48 个转移淋巴结样本中的免疫球蛋白重链 (IGH) 谱。我们的研究表明，肿瘤中的 IgG 型 B 谱系细胞浸润高于健康组织，这与患者预后的改善相关。 ACTN1、COL6A5 等基因以及粘着斑等塑造肿瘤物理结构的通路可能会影响 B 谱系细胞浸润。值得注意的是，IGH 序列被用作监测 B 细胞迁移的身份标签，并且根据我们的多区域肿瘤标本描述了它们在肿瘤内的浸润模式。该分析揭示了转移淋巴结和肿瘤之间重叠的 B 细胞克隆的增加。因此，定义了淋巴结激活指数，可以预测淋巴结转移患者的预后。这项研究引入了一种利用大规模转录组数据探测肿瘤微环境中 B 细胞浸润和迁移的新框架，同时为 ESCC 内 B 细胞免疫学提供了新的视角。
Tumor-infiltrating B-lineage cells have become predictors of prognosis and immunotherapy responses in various cancers. However, limited knowledge about their infiltration and migration patterns has hindered the understanding of their anti-tumor functions. Here, we examined the immunoglobulin heavy chain (IGH) repertoires in 496 multi-regional tumor, 107 normal tissue, and 48 metastatic lymph node samples obtained from 107 patients with esophageal squamous cell carcinoma (ESCC). Our study revealed higher IgG-type B-lineage cells infiltration in tumors than in healthy tissue, which was associated with improved patient outcomes. Genes such asACTN1,COL6A5, and pathways like focal adhesion, which shapes the physical structure of tumors, could affect B-lineage cell infiltration. Notably, the IGH sequence was used as an identity-tag to monitor B cell migration, and their infiltration schema within the tumor were depicted based on our multi-regional tumor specimens. This analysis revealed an escalation in B cell clones overlapped between metastatic lymph nodes and tumors. Therefore, the Lymph Node Activation Index was defined, which could predict the outcomes of patients with lymph node metastasis. This research introduces a novel framework for probing B cell infiltration and migration within the tumor microenvironment using large-scale transcriptome data, while simultaneously providing fresh perspectives on B cell immunology within ESCC.