Jiang Donghui, Wu Xiaoguang, Deng Yuanyuan, Yang Xi, Wang Zhiqiang, Tang Yong, He Li, He Xiaoguang
Department of Otolaryngology & Head and Neck Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
J Cell Mol Med. 2025 May;29(9):e70575. doi: 10.1111/jcmm.70575.
Head and neck squamous cell carcinoma (HNSC) exhibits profound intratumoral heterogeneity, driven by dynamic interactions between malignant cells and the tumour microenvironment (TME). Using consensus non-negative matrix factorisation (cNMF) on multi-site HNSC single-cell transcriptomes, we resolving conserved meta-programs define cellular ecosystems. Six major epithelial programmes emerged, including a differentiation-associated programme (Epi_Diff) correlated with SPDEF activity and favourable patient prognosis, and an invasive programme (Epi_pEMT) potentially controlled by TEAD4-mediated ECM remodelling, exhibiting partial EMT markers (VIM, TGFB1). Compartment-specific crosstalk analysis revealed Epi_pEMT cells may coordinate with mCAF1 fibroblasts and TAM(SPP1) through COL1A1-CD44 and SPP1-CD44 signalling, suggesting potential formation of a pro-invasive niche. Conversely, Epi_Diff cells may interact with NK/T cells through CEACAM5-CD8A and CCL5-ACKR2, and may contribute to inhibit immune infiltration. Multi-compartment correlation analysis revealed three ecosystem-level patterns: (1) Inverse association between Epi_Diff and Epi_pEMT (Spearman R = -0.43); (2) Negative correlation between mCAF1 abundance and cCAF frequency (R = -0.48); (3) TAM(SPP1) dominance inversely correlating with both TAM(C1Q) (R = -0.43) and NK/T infiltration (R = -0.36). These axes suggest a potential hierarchical ecology framework where lineage-specific polarisation and inter-compartment synergies may collectively govern disease progression.
头颈部鳞状细胞癌（HNSC）表现出显著的肿瘤内异质性，这是由恶性细胞与肿瘤微环境（TME）之间的动态相互作用驱动的。通过对多部位HNSC单细胞转录组进行共识非负矩阵分解（cNMF），我们解析了定义细胞生态系统的保守元程序。出现了六个主要的上皮程序，包括与SPDEF活性和患者良好预后相关的分化相关程序（Epi_Diff），以及可能由TEAD4介导的ECM重塑控制、表现出部分上皮-间质转化标记（VIM、TGFB1）的侵袭程序（Epi_pEMT）。特定区室的串扰分析显示，Epi_pEMT细胞可能通过COL1A1-CD44和SPP1-CD44信号与mCAF1成纤维细胞和TAM(SPP1)协调，提示可能形成促侵袭微环境。相反，Epi_Diff细胞可能通过CEACAM5-CD8A和CCL5-ACKR2与NK/T细胞相互作用，并可能有助于抑制免疫浸润。多区室相关性分析揭示了三种生态系统水平的模式：（1）Epi_Diff与Epi_pEMT之间呈负相关（斯皮尔曼相关系数R = -0.43）；（2）mCAF1丰度与cCAF频率呈负相关（R = -0.48）；（3）TAM(SPP1)优势与TAM(C1Q)（R = -0.43）和NK/T浸润（R = -0.36）均呈负相关。这些轴提示了一个潜在的分层生态框架，其中谱系特异性极化和区室间协同作用可能共同控制疾病进展。
