Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade
2024-11-11
发表期刊CANCER CELL
ISSN1535-6108
EISSN1878-3686
卷号42期号:11
DOI10.1016/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.
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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
被引频次:1[WOS]   [WOS记录]     [WOS相关记录]
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
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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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