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Blockade of IL-6 inhibits tumor immune evasion and improves anti-PD-1 immunotherapy

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资源类型：
WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Li Wenyi[1,2,3] * ; Wu Zhaokun[1,2,3] * ; Meng Weidong[3,4] * ; Zhang Chaoting[3,5] ; Cheng Mingzhen[1,3] ; Chen Yuehong[1,2,3] ; Zou Yini[1] ; Li Kejun[1,2,3] ; Lin Simin[1,6] ; Xiong Wenjun[2,3,7] ; Wang Ying[3,8] ; Lin Yixiong[2,3,9,*1] ; Ma Wenhui[1,2,3,*2] ; Zhou Weijie[1,2,3,*3] ;
机构： [1]Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [2]Departments of General Surgery, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [3]Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [4]Department of Clinical Medicine, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [5]Department of Anesthesiology, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [6]Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [7]Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No 111 Dade Road, Guangzhou, Guangdong 510120, China [8]Departments of Oncology, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [9]Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China
出处：
DOI： 10.1016/j.cyto.2022.155976
ISSN：

关键词： Colorectal cancer (CRC) IL-6 Immune evasion MHC-I molecules Anti-PD-1

摘要：
Long-standing inflammatory bowel disease predisposes to the development of colorectal cancer (CRC). Interleukin (IL) -6, a pivotal link between chronic inflammation and tumor progression, has recently been recognized as a potential therapeutic target. The effect of IL-6 on proliferation and metastasis of CRC by activating the STAT3 pathway has been widely demonstrated in recent years, but few on mediating tumor immune evasion. In this study, we found that IL-6 was remarkably overexpressed in CRC and its elevation was associated with a poor prognosis. We studied CRC tumorigenesis in vivo by inoculating MC38 tumors and induced-CRC model via AOM/DSS (azoxymethane/dextransulfate sodium) in IL-6 deficient (IL-6-/-) and wild-type (WT) mice and found that IL-6-/- mice were less susceptible to develop tumors, compared to WT mice. We detected CD8+ T cells via immunofluorescence and found they exhibit high expression in tumor of IL-6-/- mice. High level of IL-6 was found in colitis model, with down-regulation of MHC-I molecules. In in vitro experiments, we found that IL-6 may act as a negative regulator in IFNγ-STAT1-MHC-I signaling. In addition, vivo trials also confirmed that MHC-I mRNA level was negatively related to the existence of IL-6. Furthermore, the blockade of IL-6 also activated CD8+T-cell accumulation and led to the high PD-L1 expression in CRC, which can sensitize animals to anti-PD-1 therapy. Our study provides a research basis for the significant role of IL-6 in tumor evasion and highlights a novel target to improve the efficacy of immunotherapy.Copyright © 2022 Elsevier Ltd. All rights reserved.

基金：
This work was supported by the National Natural Science Foundation of China (81902970), Natural Science Foundation of Guangdong Province (No. 2017A030310115 and No. 2019A1515011325), China Postdoctoral Science Foundation (2019M650205), Guangzhou Science and Technology Collaborative Innovation Major Project (201704020071), Guangdong Key Research and Development Plan (2019B020234003).
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 3 区 医学
小类 | 3 区 生化与分子生物学 3 区 细胞生物学 3 区 免疫学
最新[2025]版：
大类 | 3 区 医学
小类 | 3 区 生化与分子生物学 3 区 细胞生物学 3 区 免疫学
JCR分区：
出版当年[2020]版：
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 IMMUNOLOGY Q3 CELL BIOLOGY
最新[2023]版：
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 CELL BIOLOGY Q2 IMMUNOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [2]Departments of General Surgery, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [3]Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [2]Departments of General Surgery, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [3]Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [9]Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, NO. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China [*1]Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China [*2]Departments of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China [*3]Departments of Pathology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China
推荐引用方式(GB/T 7714)：
Li Wenyi,Wu Zhaokun,Meng Weidong,et al.Blockade of IL-6 inhibits tumor immune evasion and improves anti-PD-1 immunotherapy[J].CYTOKINE.2022,158:doi:10.1016/j.cyto.2022.155976.
APA：
Li Wenyi,Wu Zhaokun,Meng Weidong,Zhang Chaoting,Cheng Mingzhen...&Zhou Weijie.(2022).Blockade of IL-6 inhibits tumor immune evasion and improves anti-PD-1 immunotherapy.CYTOKINE,158,
MLA：
Li Wenyi,et al."Blockade of IL-6 inhibits tumor immune evasion and improves anti-PD-1 immunotherapy".CYTOKINE 158.(2022)

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