机构：[1]Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院[5]Institute of Pediatrics of Children’s Hospital of Fudan University, The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China[6]Department of Liver Surgery and Organ Transplantation Center, Shenzhen Third People’s Hospital, Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China深圳市康宁医院深圳医学信息中心[7]Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[8]Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tumor-associated neutrophils (TANs) represent a significant barrier to the effectiveness of immune checkpoint blockade (ICB) therapy. A comprehensive understanding of TANs' regulatory mechanisms is therefore essential for predicting ICB efficacy and improving immunotherapy strategies. Our study reveals that MYO1F is selectively downregulated in neutrophils within both human cancers and murine tumor models, showing a negative correlation with ICB response. Mechanistically, MYO1F normally inhibits neutrophil immunosuppression and proliferation by restraining STAT3 activity. However, during tumorigenesis, tumor-derived TGF-beta 1 disrupts the binding of SPI1 to intron 8 of Myo1f via DNA methylation, thereby suppressing Myo1f transcription. The resultant decrease in MYO1F reprograms neutrophils into an immunosuppressive state through the STAT3-dependent signaling pathways. This immunosuppressive state further contributes to tumor microenvironment (TME) remodeling by inducing CTL exhaustion. These findings establish MYO1F as a critical regulator within TANs, highlighting its significant role in modulating ICB therapy efficacy.
基金：
National Key Research and Development Program of China [2022YFA 0912400]; National Natural Science Foundation of China [82230055]; Technology Committee of Shanghai Municipality [23DX1900302]; Innovative Research Team of High-level Local Universities in Shanghai; Shanghai Jiao Tong University Global Strategic Partnership Fund; State Key Laboratory of Medical Genomics
第一作者机构：[1]Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China
推荐引用方式(GB/T 7714)：
Qu Yingying,Liang Wenhua,Yu Mingzhu,et al.MYO1F in neutrophils is required for the response to immune checkpoint blockade therapy[J].JOURNAL OF EXPERIMENTAL MEDICINE.2025,222(6):doi:10.1084/jem.20241957.
APA：
Qu, Yingying,Liang, Wenhua,Yu, Mingzhu,Wang, Chenhui,Luo, Min...&Wang, Feng.(2025).MYO1F in neutrophils is required for the response to immune checkpoint blockade therapy.JOURNAL OF EXPERIMENTAL MEDICINE,222,(6)
MLA：
Qu, Yingying,et al."MYO1F in neutrophils is required for the response to immune checkpoint blockade therapy".JOURNAL OF EXPERIMENTAL MEDICINE 222..6(2025)
医学