Single-cell and spatial transcriptomics reveals an anti-tumor neutrophil subgroup in microwave thermochemotherapy-treated lip cancer

作者：Bing-jun Chen, Hua‐yang Fan, Xin Pang, Zeliang Shen, Rui Gao, Haofan Wang, Zhen-wei Yu, Tianjiao Li, Mao Li, Yaling Tang, Xin‐hua Liang · 发表于：International Journal of Oral Science · 年份：2025 · DOI：10.1038/s41368-025-00366-8 · 被引用次数：8 · 研究领域：Immune cells in cancer、Single-cell and spatial transcriptomics、Cancer Cells and Metastasis

Abstract Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA + TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B , activating T&NK cells and fibroblasts via IL1B - IL1R . In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2 - CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12 - CXCR4 , which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2 , which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.