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单细胞测序分析揭示了鼻咽癌原发和转移淋巴结中肿瘤生态系统的动态变化。

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

机构信息

College of Biomedical Information and Engineering, Hainan General Hospital and Hainan Affiliated Hospital, Hainan Medical University, Haikou, China.

Hainan Engineering Research Center for Health Big Data, Hainan Medical University, Haikou, China.

出版信息

J Cell Mol Med. 2024 Oct;28(19):e70137. doi: 10.1111/jcmm.70137.

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.

摘要

淋巴结转移是导致鼻咽癌(NPC)主要病因和治疗失败的原因。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 NPC 患者淋巴结转移(LNM)的生态系统仍未得到充分描述。在这里,我们整合了 8 个与 NPC LNM 相关样本中 47618 个单细胞的转录组。与原发肿瘤相比,在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、髓样细胞和 B 细胞。此外,还揭示了上皮细胞的异质性,并鉴定了几个与 NPC 患者无进展生存相关的表达程序簇。此外,我们的数据还揭示了从原发肿瘤到淋巴结转移的复杂细胞间通讯。进一步确定了在肿瘤转移中起重要作用的 CCL 信号的重排。总之,我们系统地描述了 NPC 原发肿瘤和淋巴结转移肿瘤的生态系统,这可能为改善伴有淋巴结转移的 NPC 患者的临床治疗效果提供治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c3/11467730/4fac3cec3cb2/JCMM-28-e70137-g002.jpg

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