南方科技大学知识苑(SUSTech KC): Deubiquitinase USP4 suppresses antitumor immunity by inhibiting IRF3 activation and tumor cell-intrinsic interferon response in colorectal cancer

题名	Deubiquitinase USP4 suppresses antitumor immunity by inhibiting IRF3 activation and tumor cell-intrinsic interferon response in colorectal cancer
作者	Zhou, Yi 1; Li, Huali 1; Zhang, Yaxin 1; Zhao, Enen 1; Huang, Chengmei 1; Pan, Xingyan 1; Shu, Feng 1; Liu, Zhihao 1; Tang, Na 2; Li, Fengtian 1,3; Liao, Wenting 1
通讯作者	Tang, Na; Li, Fengtian; Liao, Wenting
发表日期	2024-05-01
DOI	10.1016/j.canlet.2024.216836
发表期刊	CANCER LETTERS 影响因子和分区
ISSN	0304-3835
EISSN	1872-7980
卷号	589
摘要	Despite the approval of immune checkpoint blockade (ICB) therapy for various tumor types, its effectiveness is limited to only approximately 15% of patients with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) colorectal cancer (CRC). Approximately 80% - 85% of CRC patients have a microsatellite stability (MSS) phenotype, which features a rare T-cell infiltration. Thus, elucidating the mechanisms underlying resistance to ICB in patients with MSS CRC is imperative. In this study, we demonstrate that ubiquitin-specific peptidase 4 (USP4) is upregulated in MSS CRC tumors and negatively regulates the immune response against tumors in CRC. Additionally, USP4 represses the cellular interferon (IFN) response and antigen presentation and impairs PRR signaling-mediated cell death. Mechanistically, USP4 impedes the nuclear localization of interferon regulator Factor 3 (IRF3) by deubiquitinating the K63-polyubiquitin chain of TRAF6 and IRF3. Knockdown of USP4 enhances the infiltration of T cells in CRC tumors and overcomes ICB resistance in an MC38 syngeneic mouse model. Moreover, published datasets revealed that patients showing higher USP4 expression exhibited decreased responsiveness to anti-PD-L1 therapy. These findings highlight an essential role of USP4 in the suppression of antitumor immunity in CRC.
关键词	Colorectal cancer USP4 IRF3 Interferon response Immune suppression
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	通讯
资助项目	China Postdoctoral Science Foundation[23xkjc018] ; Natural Science Foundation of Guangdong Province[2021M693643] ; Shenzhen Science and Technology Innovation Commission[2021A1515111073] ; Science and Technology Foundation of Shenzhen[JCYJ20180301170035531] ; null[JCYJ20210324114402006]
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:001235519600001
出版者	ELSEVIER IRELAND LTD
ESI学科分类	CLINICAL MEDICINE
来源库	Web of Science
引用统计	被引频次[WOS]：2
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/788314
专题	南方科技大学第一附属医院
作者单位	1.Sun Yat Sen Univ, Guangdong Prov Clin Res Ctr Canc, Canc Ctr, State Key Lab Oncol South China, Guangzhou 510060, Peoples R China 2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Dept Pathol,Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China 3.Chengdu Med Coll, Sch Biosci & Technol, Chengdu 610500, Sichuan, Peoples R China
通讯作者单位	南方科技大学第一附属医院
推荐引用方式 GB/T 7714	Zhou, Yi,Li, Huali,Zhang, Yaxin,et al. Deubiquitinase USP4 suppresses antitumor immunity by inhibiting IRF3 activation and tumor cell-intrinsic interferon response in colorectal cancer[J]. CANCER LETTERS,2024,589.
APA	Zhou, Yi.,Li, Huali.,Zhang, Yaxin.,Zhao, Enen.,Huang, Chengmei.,...&Liao, Wenting.(2024).Deubiquitinase USP4 suppresses antitumor immunity by inhibiting IRF3 activation and tumor cell-intrinsic interferon response in colorectal cancer.CANCER LETTERS,589.
MLA	Zhou, Yi,et al."Deubiquitinase USP4 suppresses antitumor immunity by inhibiting IRF3 activation and tumor cell-intrinsic interferon response in colorectal cancer".CANCER LETTERS 589(2024).