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Combination Of STING Agonist And CXCR3 Antagonist Disrupts Immune Tolerance To Overcome Anti-PD-L1 Resistance In Lung Adenocarcinoma Under Oxidative Stress

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收录情况： ◇ SCIE

作者：
Zhu Lingling[1,2] ; Gao Honglin[2] ; Huang Shiqi[2] ; Cao Ting[3] ; Zhai Xiaoqian[1] ; Hu Jia[1] ; Wang Ting[1] ; Dong Jingsi[1] ; Liu Zelong[4,5] ; Chen Jiang[6] ; Liu Jiewei[1] ; Zhang Zhirong[2] ; Zhou Qinghua[1] ;
机构： [1]Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, China [2]Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, [3]Laboratory of Infectious Diseases and Vaccine, West China Hospital, Sichuan University, Chengdu, China [4]Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA [5]Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China [6]Department of General Surgery, Sir Run Shaw Hospital, Zhejiang University, Hangzhou, China
出处：
DOI： 10.1016/j.gene.2022.146962
ISSN：

摘要：
We investigated the role of the STING1-CXCR3 axis using database data and verified it in a mouse model bearing Lewis lung carcinoma (LLC) cells exposed to hydrogen peroxide (H2O2). Mice were treated with STING agonist liposomes (STING-Lip), anti-programmed death-ligand 1 (PD-L1), or STING-Lip+anti-PD-L1. The database data revealed that immune response pathways were enriched in patients with lung adenocarcinoma with upregulated STING1 signaling. Upregulated STING1 signaling was associated with a high abundance of immunoregulatory and effector molecules, cytokines, activated CD8+ T cells, and M1 macrophages in patients with lung adenocarcinoma. In this study, H2O2-treated LLC cells promoted an immunosuppressive microenvironment and enhanced tumor growth in mice. STING-Lip inhibited distant, untreated, and H2O2-induced LLC growth by activating systemic immunity. STING-Lip+anti-PD-L1 failed to slow distant and untreated LLC growth, whereas STING-Lip+anti-PD-L1+CXCR3 antagonist inhibited distant tumor growth in mice. The combination of STING1 activation and CXCR3 inhibition may be a novel immunotherapeutic strategy to overcome immune checkpoint inhibitor resistance in lung adenocarcinoma by activating systemic immunity in the tumor microenvironment under oxidative stress.Copyright © 2022 Elsevier B.V. All rights reserved.

基金：
This study was supported by the National Natural Science Founda￾tion (grant number 82202989), the Regional Innovation Cooperation Project of Sichuan Science and Technology Program (grant number 2021YFQ0029); Sichuan Science and Technology Program (grant number 2019YFS0111 and 2022YFS2019); the Wu Jieping Medical Foundation (grant number 312150082); the Postdoctoral Research Project of West China Hospital, Sichuan University, Chengdu, China (grant number 2021HXBH045); the Fundamental Research Funds for the Central Universities (awarded to LZ); the Special Funding for Post￾doctoral Research Projects in Sichuan Province (awarded to LZ); and the Sichuan University Postdoctoral Interdisciplinary Innovation Fund (awarded to LZ).
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外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 3 区 生物学
小类 | 3 区 遗传学
最新[2023]版：
大类 | 3 区 生物学
小类 | 3 区 遗传学
JCR分区：
出版当年[2023]版：
Q2 GENETICS & HEREDITY
最新[2023]版：
Q2 GENETICS & HEREDITY

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

第一作者：
第一作者机构： [1]Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, China [2]Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering,
通讯作者：
推荐引用方式(GB/T 7714)：
Zhu Lingling,Gao Honglin,Huang Shiqi,et al.Combination Of STING Agonist And CXCR3 Antagonist Disrupts Immune Tolerance To Overcome Anti-PD-L1 Resistance In Lung Adenocarcinoma Under Oxidative Stress[J].GENE.2023,851:doi:10.1016/j.gene.2022.146962.
APA：
Zhu Lingling,Gao Honglin,Huang Shiqi,Cao Ting,Zhai Xiaoqian...&Zhou Qinghua.(2023).Combination Of STING Agonist And CXCR3 Antagonist Disrupts Immune Tolerance To Overcome Anti-PD-L1 Resistance In Lung Adenocarcinoma Under Oxidative Stress.GENE,851,
MLA：
Zhu Lingling,et al."Combination Of STING Agonist And CXCR3 Antagonist Disrupts Immune Tolerance To Overcome Anti-PD-L1 Resistance In Lung Adenocarcinoma Under Oxidative Stress".GENE 851.(2023)

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