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Title: Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma
Authors: Nguyen, Phuong HD
Ma, Siming 
Phua, Cheryl ZJ
Kaya, Neslihan A
Lai, Hannah LH
Lim, Chun Jye
Lim, Jia Qi
Wasser, Martin 
Lai, Liyun
Tam, Wai Leong 
Lim, Tony KH
Wan, Wei Keat 
Loh, Tracy
Leow, Wei Qiang 
Pang, Yin Huei 
Chan, Chung Yip 
Lee, Ser Yee 
Cheow, Peng Chung 
Toh, Han Chong 
Ginhoux, Florent 
Iyer, Shridhar 
Kow, Alfred WC
Young Dan, Yock 
Chung, Alexander 
Goh, Brian KP 
Albani, Salvatore 
Chow, Pierce KH 
Zhai, Weiwei
Chew, Valerie 
Issue Date: Dec-2021
Publisher: Springer Science and Business Media LLC
Citation: Nguyen, Phuong HD, Ma, Siming, Phua, Cheryl ZJ, Kaya, Neslihan A, Lai, Hannah LH, Lim, Chun Jye, Lim, Jia Qi, Wasser, Martin, Lai, Liyun, Tam, Wai Leong, Lim, Tony KH, Wan, Wei Keat, Loh, Tracy, Leow, Wei Qiang, Pang, Yin Huei, Chan, Chung Yip, Lee, Ser Yee, Cheow, Peng Chung, Toh, Han Chong, Ginhoux, Florent, Iyer, Shridhar, Kow, Alfred WC, Young Dan, Yock, Chung, Alexander, Goh, Brian KP, Albani, Salvatore, Chow, Pierce KH, Zhai, Weiwei, Chew, Valerie (2021-12). Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma. Nature Communications 12 (1). ScholarBank@NUS Repository.
Abstract: AbstractThe clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic immune-ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune-ITH is associated with tumour transcriptomic-ITH, mutational burden and distinct immune microenvironments. Tumours with low immune-ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression.
Source Title: Nature Communications
ISSN: 20411723
DOI: 10.1038/s41467-020-20171-7
Appears in Collections:Staff Publications

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