Distinct Functional Metagenomic Markers Predict the Responsiveness to Anti-PD-1 Therapy in Chinese Non-Small Cell Lung Cancer Patients

doi:10.3389/fonc.2022.837525

科研成果详情

题名	Distinct Functional Metagenomic Markers Predict the Responsiveness to Anti-PD-1 Therapy in Chinese Non-Small Cell Lung Cancer Patients
作者	Fang，Chao 1,2; Fang，Wenfeng 3; Xu，Liqin 2,4; Gao，Fangfang 3; Hou，Yong 1,2; Zou，Hua 2; Ma，Yuxiang 3; Moll，Janne Marie 4; Yang，Yunpeng 3; Wang，Dan 2; Huang，Yan 3; Ren，Huahui 1,2; Zhao，Hongyun 3; Qin，Shishang 2; Zhong，Huanzi 1,2; Li，Junhua 2,5; Liu，Sheng 2; Yang，Huanming 2,6; Wang，Jian 2,6; Brix，Susanne 4; Kristiansen，Karsten 1,2,7; Zhang，Li 3
发表日期	2022-04-21
发表期刊	Frontiers in Oncology
卷号	12
摘要	Background: Programmed death 1 (PD-1) and the ligand of PD-1 (PD-L1) are central targets for immune-checkpoint therapy (ICT) blocking immune evasion-related pathways elicited by tumor cells. A number of PD-1 inhibitors have been developed, but the efficacy of these inhibitors varies considerably and is typically below 50%. The efficacy of ICT has been shown to be dependent on the gut microbiota, and experiments using mouse models have even demonstrated that modulation of the gut microbiota may improve efficacy of ICT. Methods: We followed a Han Chinese cohort of 85 advanced non-small cell lung cancer (NSCLC) patients, who received anti-PD-1 antibodies. Tumor biopsies were collected before treatment initiation for whole exon sequencing and variant detection. Fecal samples collected biweekly during the period of anti-PD-1 antibody administration were used for metagenomic sequencing. We established gut microbiome abundance profiles for identification of significant associations between specific microbial taxa, potential functionality, and treatment responses. A prediction model based on random forest was trained using selected markers discriminating between the different response groups. Results: NSCLC patients treated with antibiotics exhibited the shortest survival time. Low level of tumor-mutation burden and high expression level of HLA-E significantly reduced progression-free survival. We identified metagenomic species and functional pathways that differed in abundance in relation to responses to ICT. Data on differential enrichment of taxa and predicted microbial functions in NSCLC patients responding or non-responding to ICT allowed the establishment of random forest algorithm-adopted models robustly predicting the probability of whether or not a given patient would benefit from ICT. Conclusions: Overall, our results identified links between gut microbial composition and immunotherapy efficacy in Chinese NSCLC patients indicating the potential for such analyses to predict outcome prior to ICT.
关键词	anti-PD-1 biomarker gut microbiome immune checkpoint therapy lung cancer
DOI	10.3389/fonc.2022.837525
URL	查看来源
语种	英语English
Scopus入藏号	2-s2.0-85129672667
引用统计
文献类型	期刊论文
条目标识符	https://repository.uic.edu.cn/handle/39GCC9TT/13130
专题	个人在本单位外知识产出
通讯作者	Kristiansen，Karsten
作者单位	1.Laboratory of Genomics and Molecular Biomedicine,Department of Biology,University of Copenhagen,Copenhagen,Denmark 2.BGI-Shenzhen,Shenzhen,China 3.State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Sun Yat-Sen University Cancer Center,Guangzhou,China 4.Department of Biotechnology and Biomedicine,Technical University of Denmark,Lyngby,Denmark 5.School of Biology and Biological Engineering,South China University of Technology,Guangzhou,China 6.James D,Watson Institute of Genome Sciences,Hangzhou,China 7.Institute of Metagenomics,Qingdao-Europe Advance Institute for Life Sciences,BGI-Qingdao,Qingdao,China
推荐引用方式 GB/T 7714	Fang，Chao,Fang，Wenfeng,Xu，Liqinet al. Distinct Functional Metagenomic Markers Predict the Responsiveness to Anti-PD-1 Therapy in Chinese Non-Small Cell Lung Cancer Patients[J]. Frontiers in Oncology, 2022, 12.
APA	Fang，Chao., Fang，Wenfeng., Xu，Liqin., Gao，Fangfang., Hou，Yong., .. & Zhang，Li. (2022). Distinct Functional Metagenomic Markers Predict the Responsiveness to Anti-PD-1 Therapy in Chinese Non-Small Cell Lung Cancer Patients. Frontiers in Oncology, 12.
MLA	Fang，Chao,et al."Distinct Functional Metagenomic Markers Predict the Responsiveness to Anti-PD-1 Therapy in Chinese Non-Small Cell Lung Cancer Patients". Frontiers in Oncology 12(2022).