Single-cell and spatial transcriptomics reveals an anti-tumor neutrophil subgroup in microwave thermochemotherapy-treated lip cancer.
10.1038/s41368-025-00366-8
- Author:
Bingjun CHEN
1
;
Huayang FAN
1
;
Xin PANG
1
;
Zeliang SHEN
2
;
Rui GAO
3
;
Haofan WANG
1
;
Zhenwei YU
1
;
Tianjiao LI
1
;
Mao LI
2
;
Yaling TANG
4
;
Xinhua LIANG
5
Author Information
1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
3. University of Electronic Science and Technology of China, Chengdu, China.
4. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. tangyaling@scu.edu.cn.
5. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. lxh88866@scu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Humans;
Neutrophils/metabolism*;
Single-Cell Analysis;
Lip Neoplasms/genetics*;
Hyperthermia, Induced/methods*;
Microwaves/therapeutic use*;
Transcriptome;
Carcinoma, Squamous Cell/immunology*;
Tumor Microenvironment
- From:
International Journal of Oral Science
2025;17(1):40-40
- CountryChina
- Language:English
-
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.
