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SPP1 TAM 通过重塑淋巴结微环境调节 CXCR4 转移相关肿瘤细胞的转移定植。

SPP1 TAM Regulates the Metastatic Colonization of CXCR4 Metastasis-Associated Tumor Cells by Remodeling the Lymph Node Microenvironment.

机构信息

Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC), Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, 404100, China.

出版信息

Adv Sci (Weinh). 2024 Nov;11(44):e2400524. doi: 10.1002/advs.202400524. Epub 2024 Sep 5.

DOI:10.1002/advs.202400524
PMID:39236316
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11600252/
Abstract

Lymph node metastasis, the initial step in distant metastasis, represents a primary contributor to mortality in patients diagnosed with oral squamous cell carcinoma (OSCC). However, the underlying mechanisms of lymph node metastasis in OSCC remain incompletely understood. Here, the transcriptomes of 56 383 single cells derived from paired tissues of six OSCC patients are analyzed. This study founds that CXCR4 epithelial cells, identified as highly malignant disseminated tumor cells (DTCs), exhibited a propensity for lymph node metastasis. Importantly, a distinct subset of tumor-associated macrophages (TAMs) characterized by exclusive expression of phosphoprotein 1 (SPP1) is discovered. These TAMs may remodel the metastatic lymph node microenvironment by potentially activating fibroblasts and promoting T cell exhaustion through SPP1-CD44 and CD155-CD226 ligand-receptor interactions, thereby facilitating colonization and proliferation of disseminated tumor cells. The research advanced the mechanistic understanding of metastatic tumor microenvironment (TME) and provided a foundation for the development of personalized treatments for OSCC patients with metastasis.

摘要

淋巴结转移是远处转移的初始步骤，是导致口腔鳞状细胞癌 (OSCC) 患者死亡的主要原因。然而，OSCC 中淋巴结转移的潜在机制仍不完全清楚。在这里，分析了来自六位 OSCC 患者配对组织的 56383 个单细胞的转录组。本研究发现，CXCR4 上皮细胞作为高恶性播散性肿瘤细胞 (DTC)，表现出淋巴结转移的倾向。重要的是，发现了一个独特的肿瘤相关巨噬细胞 (TAM) 亚群，其特征是磷酸蛋白 1 (SPP1) 的特异性表达。这些 TAMs 可能通过 SPP1-CD44 和 CD155-CD226 配体-受体相互作用，潜在地激活成纤维细胞并促进 T 细胞耗竭，从而重塑转移性淋巴结微环境，促进播散性肿瘤细胞的定植和增殖。该研究推进了对转移性肿瘤微环境 (TME) 的机制理解，并为开发针对转移性 OSCC 患者的个性化治疗提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/393430a86f5b/ADVS-11-2400524-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/d899705378b2/ADVS-11-2400524-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/459d4b4c7a9f/ADVS-11-2400524-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/841aca35cc5d/ADVS-11-2400524-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/8dcb751f3774/ADVS-11-2400524-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/393430a86f5b/ADVS-11-2400524-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/3a67bc7e4654/ADVS-11-2400524-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/638d85a3e377/ADVS-11-2400524-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/d899705378b2/ADVS-11-2400524-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/f6d3530ce76f/ADVS-11-2400524-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/459d4b4c7a9f/ADVS-11-2400524-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/841aca35cc5d/ADVS-11-2400524-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf91/11600252/393430a86f5b/ADVS-11-2400524-g006.jpg

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