Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes

doi:10.1136/jitc-2021-003214

	Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes
	Chen, Xiaofeng 1,2; Wang, Deqiang 3; Liu, Jing 4; Qiu, Jingrong 5; Zhou, Jun 6; Ying, Jieer 7; Shi, Yan 4; Wang, Zhaoxia 8; Lou, Haizhou 9; Cui, Jiuwei 10
刊名	JOURNAL FOR IMMUNOTHERAPY OF CANCER
	2021-11-01
卷号	9
关键词	immunotherapy tumor microenvironment biomarkers tumor genetic markers
DOI	10.1136/jitc-2021-003214
通讯作者	Shu, Yongqian(shuyongqian@csco.org.cn)
英文摘要	Background Recently, immunotherapy with immune checkpoint inhibitors (ICIs) has shown promising efficacy in biliary tract cancer (BTC), which includes gallbladder cancer (GBC) and cholangiocarcinoma (CHOL). Understanding the association between immunotherapy outcomes and the genomic profile of advanced BTC may further improve the clinical benefits from immunotherapy. Methods Genomic tumor DNA was isolated from 98 Chinese patients with advanced BTC and used for targeted next-generation sequencing of 416 cancer-related genes to identify the genomic alterations common to advanced BTC. Thirty-four patients had received ICI camrelizumab plus gemcitabine and oxaliplatin (from the NCT03486678 trial) as a first-line treatment. Tumor-infiltrating immune cells were evaluated using immunofluorescence staining. Results KRAS and TP53 mutations were much more frequent in the advanced-stage BTC cohort than in other cohorts with mostly early stage disease. Specifically, KRAS-TP53 co-mutations were favored in advanced CHOL, with a favorable response to immunotherapy, while single KRAS mutations predicted poor prognosis and immunotherapy outcomes for CHOL. Compared with GBC, CHOL had more mutations in genes involved in KRAS signaling; a high mutation load in these genes correlated with poor immunotherapy outcomes and may subsequently cause inferior immunotherapy outcomes for CHOL relative to GBC. Furthermore, a genomic signature including 11 genes was developed; their mutated subtype was associated with poor prognosis and immunotherapy outcomes in both CHOL and GBC. Transcriptome analyses suggested immune dysfunction in the signature mutated subtype, which was validated by tumor microenvironment (TME) evaluation based on detection of immune cell infiltration. Importantly, the signature wild-type subtype with favorable TME may be an advantageous population of immunotherapy. Conclusions Genomic alterations in advanced BTC were associated with specific prognosis and immunotherapy outcomes. Combining genomic classification with TME evaluation further improved the stratification of immunotherapy outcomes.
资助项目	Jiangsu province 333 high level Talents Project ; Innovation Funds From Chinese Society Of Clinical Oncology Youth Committee[Y-Young2019-060] ; Innovation Funds From Chinese Society Of Clinical Oncology Youth Committee[Y-Young2021-0107] ; Beijing Xisike Clinical Oncology Research Foundation[Y-HR2019-0367] ; Advanced Health Talent of Six-One Project of Jiangsu Province[LGY2017069] ; Joint Research Project by Southeast University[3207027381] ; Joint Research Project by Nanjing Medical University[3207027381] ; Project of Young Medical Talents in Jiangsu Province[QNRC2016829] ; 5123 Scholar Program of the Affiliated Hospital of Jiangsu University[51232017301] ; China Postdoctoral Science Foundation[2021M693272]
WOS研究方向	Oncology ; Immunology
语种	英语
出版者	BMJ PUBLISHING GROUP
WOS记录号	WOS:000720981900004
资助机构	Jiangsu province 333 high level Talents Project ; Innovation Funds From Chinese Society Of Clinical Oncology Youth Committee ; Beijing Xisike Clinical Oncology Research Foundation ; Advanced Health Talent of Six-One Project of Jiangsu Province ; Joint Research Project by Southeast University ; Joint Research Project by Nanjing Medical University ; Project of Young Medical Talents in Jiangsu Province ; 5123 Scholar Program of the Affiliated Hospital of Jiangsu University ; China Postdoctoral Science Foundation
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/126504]
专题	中国科学院合肥物质科学研究院
通讯作者	Shu, Yongqian
作者单位	1.Nanjing Med Univ, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China 2.Jiangsu Prov Hosp, Oncol, Nanjing, Jiangsu, Peoples R China 3.Jiangsu Univ Hosp, Oncol, Nanjing, Jiangsu, Peoples R China 4.Shanghai Jiao Tong Univ, Med Sch, Affiliated Ruijin Hosp, Oncol, Shanghai, Peoples R China 5.Eastern Hepatobiliary Surg Hosp, Biol Therapy, Shanghai, Peoples R China 6.Peking Univ Canc Hosp, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China 7.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Abdominal Med Oncol, Canc Hosp, Hangzhou, Peoples R China 8.Nanjing Med Univ, Affiliated Hosp 2, Oncol, Nanjing, Jiangsu, Peoples R China 9.Zhejiang Univ, Oncol, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Zhejiang, Peoples R China 10.Jilin Univ First Hosp, Canc Ctr, Changchun, Peoples R China
推荐引用方式 GB/T 7714	Chen, Xiaofeng,Wang, Deqiang,Liu, Jing,et al. Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes[J]. JOURNAL FOR IMMUNOTHERAPY OF CANCER,2021,9.
APA	Chen, Xiaofeng.,Wang, Deqiang.,Liu, Jing.,Qiu, Jingrong.,Zhou, Jun.,...&Shu, Yongqian.(2021).Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes.JOURNAL FOR IMMUNOTHERAPY OF CANCER,9.
MLA	Chen, Xiaofeng,et al."Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes".JOURNAL FOR IMMUNOTHERAPY OF CANCER 9(2021).