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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. <jats:italic>MNDA<\/jats:italic>\n            <jats:sup>+<\/jats:sup> 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 <jats:italic>IL1B<\/jats:italic>, activating T&amp;NK cells and fibroblasts via <jats:italic>IL1B<\/jats:italic>-<jats:italic>IL1R<\/jats:italic>. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via <jats:italic>CXCL2<\/jats:italic>-<jats:italic>CXCR2<\/jats:italic> and clear N2-TANs (pro-tumor phenotype) via <jats:italic>CXCL12<\/jats:italic>-<jats:italic>CXCR4<\/jats:italic>, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, <jats:italic>MX2<\/jats:italic>, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&amp;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.<\/jats:p>","DOI":"10.1038\/s41368-025-00366-8","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T10:27:45Z","timestamp":1747132065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Single-cell and spatial transcriptomics reveals an anti-tumor neutrophil subgroup in microwave thermochemotherapy-treated lip cancer"],"prefix":"10.1038","volume":"17","author":[{"given":"Bingjun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeliang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haofan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"366_CR1","doi-asserted-by":"publisher","first-page":"104551","DOI":"10.1016\/j.oraloncology.2019.104551","volume":"102","author":"A Miranda-Filho","year":"2020","unstructured":"Miranda-Filho, A. & Bray, F. 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