Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer

doi:10.1080/21645515.2021.1891814

科研成果详情

题名	Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer
作者	Yu, Yaojun1; Zhang, Jing2; Ni, Leyi 2; Zhu, Yuesheng2; Yu, Hejie 2; Teng, Yangyang2; Lin, Limiao2; Xue, Zhanxiong2; Xue, Xiangyang3; Shen, Xian1; Song, Haiping 4; Su, Xiaoping 3; Sun, Weihong 5; Cai, Zhenzhai2
发表期刊	HUMAN VACCINES & IMMUNOTHERAPEUTICS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Colorectal cancer immunotherapy neoantigens tumor cancer vaccine
摘要	Neoantigens play a crucial role in cancer immunotherapy. However, the effectiveness and safety of neoantigen-based immunotherapies in patients with colorectal cancer (CRC), particularly in the Chinese population, have not been well studied. This study explored the feasibility and effectiveness of neoantigens in the treatment of CRC. Whole-exome sequencing (WES) and transcriptome sequencing were used to identify somatic mutations, RNA expression, and human leukocyte antigen (HLA) alleles. Neoantigen candidates were predicted, and immunogenicity was assessed. The neoantigens TSHZ3-L523P, RARA-R83H, TP53-R248W, EYA2-V333I, and NRAS-G12D from Patient 4 (PW4); TASP1-P161L, RAP1GAP-S215R, MOSPD1-V63I, and NAV2-D1973N from Patient 10 (PW10); and HAVCR2-F39V, SEC11A-R11L, SMPDL3B-T452M, LRFN3-R118Q, and ULK1-S248L from Patient 11 (HLA-A0201(+)PW11) induced a heightened neoantigen-reactive T cell (NRT) response as compared with the controls in peripheral blood lymphocytes (PBLs) isolated from patients with CRC. In addition, we identified neoantigen-containing peptides SEC11A-R11L and ULK1-S248L from HLA-A0201(+)PW11, which more effectively elicited specific CTL responses than the corresponding native peptides in PBLs isolated from HLA-A0201(+)PW11 as well as in HLA-A2.1/K-b transgenic mice. Importantly, adoptive transfer of NRTs induced by vaccination with two mutant peptides could effectively inhibit tumor growth in tumor-bearing mouse models. These data indicate that neoantigen-containing peptides with high immunogenicity represent promising candidates for peptide-mediated personalized therapy.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [3197080252]; Qingdao Science and Technology Project [19-6-1-27-nsh]; Qingdao Outstanding Health Professional Development Fund; Wenzhou Major Science and Technology Special Project from Wenzhou Science and Technology Bureau [2018ZY004]; Public Benefit Technology Research Project of Zhejiang Science and Technology Department [LGF20H160019]; Research Foundation of Academician Helin Workstation [19331103]
出版者	TAYLOR & FRANCIS INC
出版地	PHILADELPHIA
ISSN	2164-5515
EISSN	2164-554X
卷号	18 期号:1 页码:1-11
DOI	10.1080/21645515.2021.1891814
WOS类目	Biotechnology & Applied Microbiology ; Immunology
WOS研究方向	Biotechnology & Applied Microbiology ; Immunology
WOS记录号	WOS:000626860600001
收录类别	SCIE ; PUBMED ; SCOPUS
发表日期	2022-12-31
URL	查看原文
Pubmed记录号	33689574
PMC记录号	PMC8920255
Scopus记录号	2-s2.0-85102268641
引用统计	被引频次：6[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17139
专题	第二临床医学院、附属第二医院、育英儿童医院基础医学院（机能实验教学中心）
通讯作者	Su, Xiaoping; Sun, Weihong; Cai, Zhenzhai
作者单位	1.Wenzhou Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 2, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Wenzhou 325000, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Dept Oncol, Sch Basic Med, Wenzhou, Zhejiang, Peoples R China; 4.Qingdao Univ, Qingdao Cent Hosp, Affiliated Hosp 2, Dept Oncol, Qingdao, Peoples R China; 5.Qingdao Univ, Affiliated Hosp 2, Qingdao Cent Hosp, Dept Oncol,Biotherapy Ctr, Qingdao, Peoples R China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 胃肠外科
通讯作者单位	基础医学院（机能实验教学中心）; 第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 消化内科
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院; 基础医学院（机能实验教学中心）; 第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Yu, Yaojun,Zhang, Jing,Ni, Leyi,et al. Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer[J]. HUMAN VACCINES & IMMUNOTHERAPEUTICS,2022,18(1):1-11.
APA	Yu, Yaojun., Zhang, Jing., Ni, Leyi., Zhu, Yuesheng., Yu, Hejie., ... & Cai, Zhenzhai. (2022). Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer. HUMAN VACCINES & IMMUNOTHERAPEUTICS, 18(1), 1-11.
MLA	Yu, Yaojun,et al."Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer".HUMAN VACCINES & IMMUNOTHERAPEUTICS 18.1(2022):1-11.