单细胞和空间转录组学揭示了甲状腺癌症进展中的细胞状态转变和微环境重塑
Cell-state transitions and microenvironmental remodeling in thyroid cancer progression revealed by single-cell and spatial transcriptomics.
摘要(中文译文)
甲状腺癌涵盖从惰性分化型肿瘤到转移性、放射性碘难治性及未分化性疾病。传统组织学和分子分型可界定主要风险组，但无法解析伴随疾病进展的细胞状态和空间异质性。本综述整合了近年来在局限性甲状腺乳头状癌（PTC）、转移性或放射性碘难治性分化型甲状腺癌（DTC）、低分化甲状腺癌（PDTC）及未分化甲状腺癌（ATC）中开展的单细胞RNA测序、空间转录组学及验证性研究。现有证据表明，疾病进展伴随恶性上皮状态、基质区域和免疫模式的改变。恶性上皮细胞从滤泡样程序向部分EMT样、去分化样及未分化状态转变；基质改变包括侵袭性边界、僵硬的瘤周基质以及CAF/ECM丰富的低分化区域；免疫模式在进展性PTC、惰性淋巴组织化肿瘤和髓系细胞丰富的ATC之间存在差异。有功能学支持的实例，包括POSTN-IL-4信号传导、CCL20/CXCL5巨噬细胞-肿瘤相互信号及SIGLEC15相关检查点信号，展示了这些技术如何产生治疗假说。然而，大多数数据集为横断面研究，许多配体-受体相互作用仍为计算预测的候选对象。我们利用现有证据将上皮可塑性、基因组背景、基质区域、免疫重塑及候选细胞-细胞相互作用与不同疾病状态相关联，同时将观察到的关联与已确立的逐步肿瘤演化区分开来。本综述重点阐述了需要功能和临床验证的机制及治疗假说。
Abstract
Thyroid cancer ranges from indolent differentiated tumors to metastatic, radioiodine-refractory and anaplastic disease. Conventional histology and molecular classification define major risk groups but do not resolve the cell states and spatial heterogeneity that accompany progression. This review integrates recent single-cell RNA sequencing, spatial transcriptomics and validation studies across localized papillary thyroid carcinoma (PTC), metastatic or radioiodine-refractory differentiated thyroid cancer (DTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). Current evidence indicates that progression is accompanied by changes in malignant epithelial states, stromal regions and immune patterns. Malignant epithelial cells shift from follicular-like programs toward partial EMT-like, dedifferentiation-like and anaplastic states; stromal changes include invasive borders, stiff peritumoral matrix and CAF/ECM-rich poorly differentiated regions; and immune patterns differ between progressive PTC, indolent lymphoid-organized tumors and myeloid-rich ATC. Functionally supported examples, including POSTN-IL-4 signaling, CCL20/CXCL5 macrophage-tumor reciprocal signals and SIGLEC15-associated checkpoint signaling, show how these technologies can generate therapeutic hypotheses. Yet most datasets are cross-sectional, and many ligand-receptor interactions remain computational candidates. We use the available evidence to relate epithelial plasticity, genomic context, stromal regions, immune remodeling and candidate cell-cell interactions across disease states, while separating observed associations from established stepwise tumor evolution. This synthesis highlights mechanisms and therapeutic hypotheses that require functional and clinical validation.
如何引用
AMA
Xin Wang, Deshuang Tao, Jinming Xu, Wensi Liu, Zhiwu Ji, Hairui Zhou, et al. Cell-state transitions and microenvironmental remodeling in thyroid cancer progression revealed by single-cell and spatial transcriptomics.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1904196.
APA
Xin Wang, Deshuang Tao, Jinming Xu, Wensi Liu, Zhiwu Ji, Hairui Zhou, et al (2026). Cell-state transitions and microenvironmental remodeling in thyroid cancer progression revealed by single-cell and spatial transcriptomics.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1904196
GB/T 7714
Xin Wang, Deshuang Tao, Jinming Xu, Wensi Liu, Zhiwu Ji, Hairui Zhou, et al. Cell-state transitions and microenvironmental remodeling in thyroid cancer progression revealed by single-cell and spatial transcriptomics.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1904196.
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