Tumor cell-derived microparticles induced by methotrexate augment T-cell antitumor responses by down-regulating expression of PD-1 in neutrophils

doi:10.1158/2326-6066.CIR-22-0595

科研成果详情

题名	Tumor cell-derived microparticles induced by methotrexate augment T-cell antitumor responses by down-regulating expression of PD-1 in neutrophils
作者	Xu, Pingwei1; Zhang, Xiaojie2; Chen, Kai 3; Zhu, Meng 4; Jia, Ru 4; Zhou, Qingwei5; Yang, Jintao 1; Dai, Juqin1; Jin, Yuepeng3; Shi, Keqing1
发表日期	2023-04
发表期刊	Cancer immunology research 影响因子和分区
语种	英语
原始文献类型	Journal Article
其他关键词	CANCER ; RESISTANCE ; BLOCKADE ; SUCCESS
摘要	Neutrophils act as a "double-edged sword" in the tumor microenvironment (TME) by either supporting or suppressing tumor progression. Thus, eliciting a neutrophil antitumor response remains challenging. Here, we showed that tumor cell-derived microparticles induced by methotrexate (MTX-MP) acts as an immunotherapeutic agent to activate neutrophils, increasing the tumor-killing effect of the cells and augmenting T-cell antitumor responses. We found that lactate induced tumor-associated neutrophils (TANs) to elevate expression of PD-1 and that PD-1+ neutrophils had the properties of N2 neutrophils and suppressed T-cell activation through PD-1/PD-L1 signaling. By performing ex vivo experiments, we found that MTX-MPs-activated neutrophils had reduced surface expression of PD-1 as a result of PD-1 internalization and degradation in the lysosomes, leading to the cells showing a decreased capacity to suppress T-cell responses. In addition, we also found that MTX-MP-activated neutrophils released neutrophil elastase which could kill tumor cells and disrupt tumor stroma, leading to increased T-cell infiltration. Furthermore, using a combination of anti-PD-L1 and MTX-MPs, we observed that long-term survival increased in a mouse model of lung cancer. Collectively, these findings highlight the potential use of a combination of anti-PD-L1 and MTX-MPs to enhance the therapeutic effect of anti-PD-L1 alone.
资助项目	National Natural Science Foundation of China [82101926]; Medical Health Science and Technology Project of Zhejiang Provincial Health Commission [2023RC208]; Provinces and Ministries Cocontribution of Zhejiang, China [WKJ-ZJ-2035]; Key Projects of Wenzhou Science and Technology Bureau [ZY2019016]
出版者	AMER ASSOC CANCER RESEARCH
ISSN	2326-6066
EISSN	2326-6074
卷号	11 期号:4 页码:501-514
DOI	10.1158/2326-6066.CIR-22-0595
页数	14
WOS类目	Oncology ; Immunology
WOS研究方向	Oncology ; Immunology
WOS记录号	WOS:000967343300001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	36758174
SCOPUSEID	2-s2.0-85151575438
自科自定义期刊分类	T3(B)类
通讯作者地址	[Xu, Pingwei]Translational Medicine Laboratory,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Shi, Keqing]Translational Medicine Laboratory,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Jin, Yuepeng]Department of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Medicine (all)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/172939
专题	附属第一医院_产科药学院（分析测试中心）第一临床医学院（信息与工程学院）、附属第一医院
通讯作者	Xu, Pingwei; Jin, Yuepeng; Shi, Keqing
作者单位	1.Translational Medicine Laboratory,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Department of Obstetrics,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.Department of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 4.The First Clinical Medical College,Wenzhou Medical University,Wenzhou,China; 5.School of Pharmaceutical Science,Wenzhou Medical University,Zhejiang,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Xu, Pingwei,Zhang, Xiaojie,Chen, Kai,et al. Tumor cell-derived microparticles induced by methotrexate augment T-cell antitumor responses by down-regulating expression of PD-1 in neutrophils[J]. Cancer immunology research,2023,11(4):501-514.
APA	Xu, Pingwei., Zhang, Xiaojie., Chen, Kai., Zhu, Meng., Jia, Ru., ... & Shi, Keqing. (2023). Tumor cell-derived microparticles induced by methotrexate augment T-cell antitumor responses by down-regulating expression of PD-1 in neutrophils. Cancer immunology research, 11(4), 501-514.
MLA	Xu, Pingwei,et al."Tumor cell-derived microparticles induced by methotrexate augment T-cell antitumor responses by down-regulating expression of PD-1 in neutrophils".Cancer immunology research 11.4(2023):501-514.