干旱区生态环境知识资源中心(Arid): Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival

Arid

DOI	10.1186/s13046-021-02034-1
	Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival
	Cho, Eun Jeong; Kim, Minsuh; Jo, Daum; Kim, Jihye; Oh, Ji-Hye; Chung, Hee Chul; Lee, Sun-hye; Kim, Deokhoon; Chun, Sung-Min; Kim, Jihun; Lee, Hyeonjin; Kim, Tae Won; Yu, Chang Sik; Sung, Chang Ohk; Jang, Se Jin
通讯作者	Sung, CO ; Jang, SJ (corresponding author), Asan Med Ctr, Asan Inst Life Sci, Asan Ctr Canc Genome Discovery, Seoul, South Korea.
来源期刊	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
EISSN	1756-9966
出版年	2021
卷号	40 期号:1
英文摘要	BackgroundThe intrinsic immuno-ge7nomic characteristics of colorectal cancer cells that affect tumor biology and shape the tumor immune microenvironment (TIM) are unclear.MethodsWe developed a patient-derived colorectal cancer organoid (CCO) model and performed pairwise analysis of 87 CCOs and their matched primary tumors. The TIM type of the primary tumor was classified as immuno-active, immuno-exhausted, or immuno-desert.ResultsThe gene expression profiles, signaling pathways, major oncogenic mutations, and histology of the CCOs recapitulated those of the primary tumors, but not the TIM of primary tumors. Two distinct intrinsic molecular subgroups of highly proliferative and mesenchymal phenotypes with clinical significance were identified in CCOs with various cancer signaling pathways. CCOs showed variable expression of cancer-specific immune-related genes such as those encoding HLA-I and HLA-II, and molecules involved in immune checkpoint activation/inhibition. Among these genes, the expression of HLA-II in CCOs was associated with favorable patient survival. K-means clustering analysis based on HLA-II expression in CCOs revealed a subgroup of patients, in whom cancer cells exhibited Intrinsically Immunogenic Properties (Ca-IIP), and were characterized by high expression of signatures associated with HLA-I, HLA-II, antigen presentation, and immune stimulation. Patients with the Ca-IIP phenotype had an excellent prognosis, irrespective of age, disease stage, intrinsic molecular type, or TIM status. Ca-IIP was negatively correlated with intrinsic E2F/MYC signaling. Analysis of the correlation between CCO immuno-genotype and TIM phenotype revealed that the TIM phenotype was associated with microsatellite instability, Wnt/beta -catenin signaling, APC/KRAS mutations, and the unfolded protein response pathway linked to the FBXW7 mutation in cancer cells. However, Ca-IIP was not associated with the TIM phenotype.ConclusionsWe identified a Ca-IIP phenotype from a large set of CCOs. Our findings may provide an unprecedented opportunity to develop new strategies for optimal patient stratification in this era of immunotherapy.
英文关键词	Colorectal cancer Organoids Gene expression Intrinsic HLA-II Immuno-genomic Microenvironment Prognosis
类型	Article
语种	英语
开放获取类型	gold, Green Published
收录类别	SCI-E
WOS记录号	WOS:000675233700002
WOS关键词	HUMAN COLON ; EXPRESSION ; TUMOR ; GENE ; MUTATIONS ; PHENOTYPE ; CARCINOMA ; EXPANSION ; PATTERNS ; BIOBANK
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/363862
作者单位	[Cho, Eun Jeong; Kim, Minsuh; Jo, Daum; Oh, Ji-Hye; Chung, Hee Chul; Lee, Sun-hye; Kim, Deokhoon; Chun, Sung-Min; Kim, Jihun; Lee, Hyeonjin; Sung, Chang Ohk; Jang, Se Jin] Asan Med Ctr, Asan Inst Life Sci, Asan Ctr Canc Genome Discovery, Seoul, South Korea; [Cho, Eun Jeong; Oh, Ji-Hye; Sung, Chang Ohk; Jang, Se Jin] Univ Ulsan, Asan Med Ctr, Asan Med Inst Convergence Sci & Technol, Coll Med,Dept Med Sci, Seoul, South Korea; [Kim, Jihye] Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea; [Kim, Deokhoon; Chun, Sung-Min; Kim, Jihun; Sung, Chang Ohk; Jang, Se Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea; [Kim, Tae Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea; [Yu, Chang Sik] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Colon & Rectal Surg, Seoul, South Korea; [Jang, Se Jin] OncoClew Life Sci Co Ltd, Seoul, South Korea
推荐引用方式 GB/T 7714	Cho, Eun Jeong,Kim, Minsuh,Jo, Daum,et al. Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival[J],2021,40(1).
APA	Cho, Eun Jeong.,Kim, Minsuh.,Jo, Daum.,Kim, Jihye.,Oh, Ji-Hye.,...&Jang, Se Jin.(2021).Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,40(1).
MLA	Cho, Eun Jeong,et al."Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 40.1(2021).