Hepatobiliary Tumor Organoids Reveal HLA Class I Neoantigen Landscape and Antitumoral Activity of Neoantigen Peptide Enhanced with Immune Checkpoint Inhibitors

doi:10.1002/advs.202105810

	Hepatobiliary Tumor Organoids Reveal HLA Class I Neoantigen Landscape and Antitumoral Activity of Neoantigen Peptide Enhanced with Immune Checkpoint Inhibitors
	Wang, Wenwen 1; Yuan, Tinggan2,3,4 ; Ma, Lili2,3,4 ; Zhu, Yanjing 5,6; Bao, Jinxia 7; Zhao, Xiaofang 1; Zhao, Yan 8; Zong, Yali 8; Zhang, Yani 8; Yang, Shuai 1; Qiu, Xinyao 1; Shen, Siyun 5,6; Wu, Rui 9; Wu, Tong 5,6; Wang, Hongyang 1,5,6; Gao, Dong 4,10,11; Wang, Peng2,3,4 ; Chen, Lei 1,6,12,13
	2022-08-05
发表期刊	ADVANCED SCIENCE (IF:14.3[JCR-2023],16.3[5-Year])
EISSN	2198-3844
发表状态	已发表
DOI	10.1002/advs.202105810
摘要	Neoantigen-directed therapy lacks preclinical models recapitulating neoantigen characteristics of original tumors. It is urgent to develop a platform to assess T cell response for neoantigen screening. Here, immunogenic potential of neoantigen-peptides of tumor tissues and matched organoids (n = 27 pairs) are analyzed by Score tools with whole genome sequencing (WGS)-based human leukocyte antigen (HLA)-class-I algorithms. The comparisons between 9203 predicted neoantigen-peptides from 2449 mutations of tumor tissues and 9991 ones from 2637 mutations of matched organoids demonstrate that organoids preserved majority of genetic features, HLA alleles, and similar neoantigen landscape of original tumors. Higher neoantigen load is observed in tumors with early stage. Multiomics analysis combining WGS, RNA-seq, single-cell RNA-seq, mass spectrometry filters out 93 candidate neoantigen-peptides with strong immunogenic potential for functional validation in five organoids. Immunogenic peptides are defined by inducing increased CD107aCD137IFN-gamma expressions and IFN-gamma secretion of CD8 cells in flow cytometry and enzyme-linked immunosorbent assay assays. Nine immunogenic peptides shared by at least two individuals are validated, including peptide from TP53(R90S). Organoid killing assay confirms the antitumor activity of validated immunogenic peptide-reactive CD8 cells, which is further enhanced in the presence of immune checkpoint inhibitors. The study characterizes HLA-class-I neoantigen landscape in hepatobiliary tumor, providing practical strategy with tumor organoid model for neoantigen-peptide identification in personalized immunotherapy.
关键词	immune checkpoint inhibitor multiomics analysis neoantigen patient derived hepatobiliary tumor organoid TP53
URL	查看原文
收录类别	SCI ; EI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China["U21A20376",82102871,81988101,81903184,81790633,81830054] ; Innovation Program of Shanghai Municipal Education Commission[2019-01-07-00-07-E00065] ; National Science Foundation of Shanghai["21XD1404600","21JC1406600",22140901000] ; China Postdoctoral Science Foundation[2020M671007]
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
WOS类目	Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS记录号	WOS:000806006400001
出版者	WILEY
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/195054
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_王鹏组
通讯作者	Wang, Hongyang; Gao, Dong; Wang, Peng; Chen, Lei
作者单位	1.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai Canc Ctr, Shanghai 200032, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Computat Biol, Shanghai 200031, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China 6.Natl Ctr Liver Canc, Shanghai 200441, Peoples R China 7.Nanjing Univ, Sch Med, Nanjing 210093, Peoples R China 8.Fudan Univ, Inst Metab & Integrat Biol, Shanghai 200433, Peoples R China 9.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Biliary Surg 1, Shanghai 200438, Peoples R China 10.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Shanghai Key Lab Mol Androl,State Key Lab Cell Bi, Shanghai 200031, Peoples R China 11.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China 12.Minist Educ, Key Lab Signaling Regulat & Targeting Therapy Liv, Shanghai 200438, Peoples R China 13.Shanghai Key Lab Hepatobiliary Tumor Biol EHBH, Shanghai 200438, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Wang, Wenwen,Yuan, Tinggan,Ma, Lili,et al. Hepatobiliary Tumor Organoids Reveal HLA Class I Neoantigen Landscape and Antitumoral Activity of Neoantigen Peptide Enhanced with Immune Checkpoint Inhibitors[J]. ADVANCED SCIENCE,2022.
APA	Wang, Wenwen.,Yuan, Tinggan.,Ma, Lili.,Zhu, Yanjing.,Bao, Jinxia.,...&Chen, Lei.(2022).Hepatobiliary Tumor Organoids Reveal HLA Class I Neoantigen Landscape and Antitumoral Activity of Neoantigen Peptide Enhanced with Immune Checkpoint Inhibitors.ADVANCED SCIENCE.
MLA	Wang, Wenwen,et al."Hepatobiliary Tumor Organoids Reveal HLA Class I Neoantigen Landscape and Antitumoral Activity of Neoantigen Peptide Enhanced with Immune Checkpoint Inhibitors".ADVANCED SCIENCE (2022).