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Nguyen, Phuong H D; Ma, Siming; Phua, Cheryl Z J; Kaya, Neslihan A; Lai, Hannah L H; Lim, Chun Jye; Lim, Jia Qi; Wasser, Martin; Lai, Liyun; Tam, Wai Leong; Lim, Tony K H; 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 W C; Young Dan, Yock; Chung, Alexander; Bonney, Glen K; Goh, Brian K P; Albani, Salvatore; Chow, Pierce K H; Zhai, Weiwei; Chew, Valerie
Nature communications, 01/2021, Volume: 12, Issue: 1Journal Article
The 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.
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