ArticleCell reports. Medicine2026
Checkpoint blockade-related CNS adverse events are characterized by neurotoxic T helper cells with sustained neuroantigen reactivity.
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Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2citing papers in PubMed
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Who cites it
2 citing papers in PubMed.
- Spatial Transcriptomics Reveals a T Cell-Mediated Microglial Activation Axis of Immune Checkpoint Inhibition-Related Adverse Events in the Brain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neurological Adverse Events Associated With Immune Checkpoint Inhibitors Identified Through Disproportionality Analysis of the FDA Adverse Event Reporting System.Cancer medicine · 2026Article
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Authors and funding
39 authors.
Yifei MaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Institute of Abdominal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Fujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center Binhai Campus of the First Affiliated Hospital, Fuiian Medical University, Fuzhou, China.
Ao ZhangDepartment of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Jiacai LinDepartment of Neurology, Hainan Hospital of Chinese PLA General Hospital, Sanya, China.
Fadian DingDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Institute of Abdominal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Fujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center Binhai Campus of the First Affiliated Hospital, Fuiian Medical University, Fuzhou, China.
Xinjia WangDepartment of Orthopedics and Spine Surgery, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China; Department of Orthopedics and Spine Surgery, Cancer Hospital of Shantou University Medical College, Shantou, China.
Weidong WangDepartment of Orthopedics and Spine Surgery, Cancer Hospital of Shantou University Medical College, Shantou, China.
Guangmin JianDepartment of Clinical Laboratory & Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Jingyao ZhangDepartment of Medicine, Nuvance Health Danbury Hospital, Danbury, CT, USA.
Pengfei ZhuDepartment of Clinical Laboratory & Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Yue MaDepartment of Laboratory Medicine, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, China.
Jun LvDepartment of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Hongjun ZhengXLifeSc, Ltd, Guangzhou, China.
Jin LiDepartment of Anesthesiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China.
Tong WuDepartment of Ophthalmology, Chinese PLA General Hospital Hainan Branch, Sanya, China.
Jiling ZengState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Nuclear Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Yongluo JiangState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Nuclear Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Yiwei XuDepartment of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, China.
Xiajie LyuInternal Medicine Department, Jacobi Medical Center, 1400 Pelham Play S, Bronx, NY, USA.
Youlong WangDepartment of General Surgery, Hainan Hospital of People's Liberation Army General Hospital, Sanya, China.
Yiming LiDepartment of Neurosurgery, Beijing Tiantan Hospital Capital Medical University, Beijing, China.
Nianqi LiuFaculty of Psychology, Institute of Educational Science, Huazhong University of Science and Technology, Wuhan, China.
Zong-Qing ZhengDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Neurosurgery, Binhai Branch of National Regional Medical Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Yu Si NiuAcute Communicable Disease Epidemiology Division, Dallas County Health and Human Services, Dallas, TX, USA.
Zhenyun GuoDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Institute of Abdominal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Fujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center Binhai Campus of the First Affiliated Hospital, Fuiian Medical University, Fuzhou, China.
Ningnan FangDepartment of Orthopedics and Spine Surgery, Cancer Hospital of Shantou University Medical College, Shantou, China.
Wei JiangFujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China.
Lihong WangFujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Jiahao ChenFujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China.
Mengqin YuanFujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China.
Qi HuangDepartment of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Jinjian LiDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Jun LuDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Bocen ChenKey Laboratory of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, China.
Tong HuangDepartment of General Surgery, General Hospital of XinJiang Military Command, Urumqi, China.
Tingting HeDepartment of Thoracic Surgery, The First People's Hospital of Shangqiu City Affiliated to Xinxiang Medical University, Shangqiu, China.
Guanqing ZhongDepartment of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: zhonggq@sysucc.org.cn.
Rui LiDepartment of Neurology of First Affiliated Hospital, Institute of Neuroscience, Fujian Medical University, Fuzhou, China. Electronic address: lirui158@gmail.com.
Haizhou LiuFujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China. Electronic address: liuhaizhou@fjmu.edu.cn.
Shangeng WengDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Institute of Abdominal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Fujian Provincial Key Laboratory of Immunotherapy for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center Binhai Campus of the First Affiliated Hospital, Fuiian Medical University, Fuzhou, China. Electronic address: shangeng@sina.com.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immune-related adverse events of central nervous system (irAEs-CNS) are rare yet life-threatening complications arising from immune checkpoint inhibitor therapies, with no effective treatments. The intracranial immune landscape in irAE-CNS remains poorly characterized. Through longitudinal multi-omics profiling of cerebrospinal fluid from three independent clinical cohorts-combined with serial cerebral positron emission tomography/computed tomography (PET/CT) imaging, neurofunctional assessments, and 15-month clinical follow-up, we identify a defined proinflammatory memory T helper cell population specific to irAEs-CNS. These cells co-secrete six signature inflammatory mediators (poly6+ cells) linked to interleukin (IL)-17-driven pathways, exhibit persistent neuroantigen reactivity, and could induce neuron apoptosis. Notably, NMDAR1-specific poly6+ cells are correlated with intracranial inflammation states and clinical outcomes of the disease. Therapeutically, inhibition of IL-17-a key cytokine of poly6+ cells-significantly improves irAE-CNS outcomes without compromising overall survival rates. Our study uncovers neuroantigen-specific proinflammatory Th cells as central drivers of irAE-CNS pathogenesis, offering mechanistic insights and potential therapeutic targets for this debilitating condition.
Indexed as
AntigensImmune Checkpoint InhibitorsT-Lymphocytes, Helper-InducerAnimalsFemaleHumansInterleukin-17MaleNeuronsAntigensImmune Checkpoint InhibitorsInterleukin-17clinical neurological testingimmune-related adverse events of central nervous systemmulti-omics of cerebrospinal fluidpersistent neuroantigen reactivity
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