| Literature DB >> 33431814 |
Phuong H D Nguyen1, Siming Ma2, Salvatore Albani1, Pierce K H Chow3,4,5, Weiwei Zhai6,7,8, Valerie Chew9, Cheryl Z J Phua2, Neslihan A Kaya2,10, Hannah L H Lai2, Chun Jye Lim1, Jia Qi Lim2, Martin Wasser1, Liyun Lai1, Wai Leong Tam2,10,11,12, Tony K H Lim13,14, Wei Keat Wan13,14, Tracy Loh13,14, Wei Qiang Leow13,14, Yin Huei Pang15, Chung Yip Chan14,16,17, Ser Yee Lee14,16,17, Peng Chung Cheow14,16,17, Han Chong Toh14,16, Florent Ginhoux1,18, Shridhar Iyer19, Alfred W C Kow19, Yock Young Dan20, Alexander Chung14,16,17, Glen K Bonney19, Brian K P Goh14,16,17.
Abstract
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.Entities:
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Year: 2021 PMID： 33431814 PMCID： PMC7801667 DOI： 10.1038/s41467-020-20171-7
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919