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Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade | |
Minjie Fu1,2,3,4,5; Jiaxu Zhao1,6; Licheng Zhang1,2,3,4,5; Zhewei Sheng1,2,3,4,5; Xiaohui Li1,6; Fufang Qiu1,2,3,4,5; Yuan Feng1,2,3,4,5; Muyuan You1,2,3,4,5; Hao Xu1,2,3,4,5; Jinsen Zhang1,2,3,4,5; Rui Zeng1,6; Yang Huang1,6; Cheng Li6; Wenhan Chen1,6; Zheng Chen1,2,3,4,5; Haitao Peng1,6; Longzhi Li7; Yonghe Wu (吴永和)8; Dan Ye1,9; Yudan Chi1,6; Wei Hua1,2,3,4,5; Ying Mao1,2,3,4,5,10
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2024-11-11 | |
发表期刊 | CANCER CELL |
ISSN | 1535-6108 |
EISSN | 1878-3686 |
卷号 | 42期号:11 |
DOI | 10.1016/j.ccell.2024.09.012 |
摘要 | Lung cancer brain metastasis (LCBM) poses a significant clinical challenge due to acquired resistance to tyrosine kinase inhibitor (TKI) treatment. To elucidate its underlying mechanisms, we employed single-cell RNA sequencing analysis on surgically obtained LCBM samples with diverse genetic backgrounds and TKI treatment histories. Our study uncovers that TKI treatment elevates the immune checkpoint CTLA4 expression in T cells, promoting an immune-suppressive microenvironment. This immunomodulation is initiated by tumor-derived HMGB1 in response to TKIs. In LCBM syngeneic murine models with TKI-sensitive or TKI-resistant EGFR mutations, combining CTLA4 blockade with TKIs demonstrates enhanced efficacy over TKI monotherapy or TKIs with PD1 blockade. These findings provide insights into the TKI resistance mechanisms and highlight the potential of CTLA4 blockade in effectively overcoming TKI resistance in LCBM. |
URL | 查看原文 |
收录类别 | SCI |
语种 | 英语 |
资助项目 | CAMS Innovation Fund for Medical Sciences (CIFMS)["2022-I2M-CT-B-112","2019-I2M-5-008"] ; Ministry of Science and Technology of China[2022YFA1106400] ; National Natural Science Foundation of China["82072784","82072785","82273304","82303437","32200640"] ; National Key R&D Program of China["2022YFC2406703","2022YFC 3401600"] ; Clinical Research Plan of Shanghai Hospital Development Center[SHDC2020CR5004] ; Natural Science Foundation of Shanghai[21ZR14 03400] ; Shanghai Municipal of Science and Technology Project[20JC1 419500] |
WOS研究方向 | Oncology ; Cell Biology |
WOS类目 | Oncology ; Cell Biology |
WOS记录号 | WOS:001356199500001 |
出版者 | CELL PRESS |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/433557 |
专题 | 免疫化学研究所_特聘教授组_刘海坤组 |
共同第一作者 | Jiaxu Zhao |
通讯作者 | Yudan Chi; Wei Hua; Ying Mao |
作者单位 | 1.Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China 2.National Center for Neurological Disorders, Shanghai 200040, China 3.Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai 200040, China 4.Neurosurgical Institute of Fudan University, Shanghai 200040, China 5.Shanghai Clinical Medical Center of Neurosurgery, Shanghai 200040, China 6.Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai 200032, China 7.Department of General Surgery, Jing’an District Central Hospital of Shanghai, Huashan Hospital, Fudan University, Shanghai 200042, China 8.Shanghai Institute for Advanced Immunochemical Studies (SIAIS), Shanghai Tech University, Shanghai 201210, China 9.Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China 10.Research Unit of New Technologies of Micro-Endoscopy Combination in Skull Base Surgery (2018RU008), Chinese Academy of Medical Sciences, Beijing, China |
推荐引用方式 GB/T 7714 | Minjie Fu,Jiaxu Zhao,Licheng Zhang,et al. Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade[J]. CANCER CELL,2024,42(11). |
APA | Minjie Fu.,Jiaxu Zhao.,Licheng Zhang.,Zhewei Sheng.,Xiaohui Li.,...&Ying Mao.(2024).Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade.CANCER CELL,42(11). |
MLA | Minjie Fu,et al."Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade".CANCER CELL 42.11(2024). |
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