Single-cell sequencing analysis reveals the dynamic tumour ecosystems of primary and metastatic lymph nodes in nasopharyngeal carcinoma

Dahua Xu, Nihui Zhang, Yutong Shen, Dehua Zheng, Zhizhou Xu, Peihu Li, Jiale Cai, Guanghui Tian, Qingchen Wei, Hong Wang, Hongyan Jiang, Meng Cao, Bo Wang, Kongning Li
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Abstract

Lymph node metastasis contributed to the leading cause and treatment failure in nasopharyngeal carcinoma (NPC). The microenvironment and the cellular communications of lymph node metastasized tumours determine the tumour progression and therapeutic effect, but the ecosystems about the lymph node metastasis (LNM) for NPC patients remain poorly characterized. Here, we integrated the transcriptomes of 47,618 single cells from eight samples related to NPC LNM. The dynamic immune ecosystems and immunosuppressive microenvironment including T cells, myeloid cells and B cells were observed in the lymph node metastatic samples compared with primary tumours. Additionally, the heterogeneity of epithelial cells was also revealed, and several clusters with expression programs that were associated with the progression-free survival of NPC patients were identified. Additionally, our data revealed the complex intercellular communications from primary to lymph node metastasis. The rewiring of CCL signalling which plays an important role in tumour metastasis was further identified. Altogether, we systematically characterized the ecosystem of NPC primary and lymph node metastasized tumours, which may shed light on the development of a therapeutic strategy to improve clinical outcomes of NPC patients with lymph node metastasis.

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单细胞测序分析揭示鼻咽癌原发和转移淋巴结的动态肿瘤生态系统
淋巴结转移是鼻咽癌治疗失败的主要原因。淋巴结转移肿瘤的微环境和细胞通讯决定了肿瘤的进展和治疗效果,但鼻咽癌患者淋巴结转移(LNM)的生态系统仍然特征不清。在这里,我们整合了来自八个与鼻咽癌淋巴结转移相关样本的 47,618 个单细胞的转录组。与原发肿瘤相比,淋巴结转移样本中观察到了动态免疫生态系统和免疫抑制微环境,包括T细胞、骨髓细胞和B细胞。此外,我们还发现了上皮细胞的异质性,并确定了几个与鼻咽癌患者无进展生存期相关的表达程序簇。此外,我们的数据还揭示了从原发性淋巴结转移到淋巴结转移的复杂细胞间通信。我们还进一步发现了在肿瘤转移过程中发挥重要作用的CCL信号的重新连接。总之,我们系统地描述了鼻咽癌原发和淋巴结转移肿瘤的生态系统,这可能有助于制定治疗策略,改善淋巴结转移鼻咽癌患者的临床预后。
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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