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Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma

Author

Listed:
  • Phuong H. D. Nguyen

    (Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre)

  • Siming Ma

    (Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR))

  • Cheryl Z. J. Phua

    (Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR))

  • Neslihan A. Kaya

    (Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)
    Nanyang Technological University Singapore)

  • Hannah L. H. Lai

    (Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR))

  • Chun Jye Lim

    (Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre)

  • Jia Qi Lim

    (Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR))

  • Martin Wasser

    (Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre)

  • Liyun Lai

    (Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre)

  • Wai Leong Tam

    (Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)
    Nanyang Technological University Singapore
    Cancer Science Institute of Singapore, National University of Singapore
    National University of Singapore)

  • Tony K. H. Lim

    (Singapore General Hospital
    Duke-NUS Medical School)

  • Wei Keat Wan

    (Singapore General Hospital
    Duke-NUS Medical School)

  • Tracy Loh

    (Singapore General Hospital
    Duke-NUS Medical School)

  • Wei Qiang Leow

    (Singapore General Hospital
    Duke-NUS Medical School)

  • Yin Huei Pang

    (National University Hospital Singapore)

  • Chung Yip Chan

    (Duke-NUS Medical School
    National Cancer Centre
    Singapore General Hospital)

  • Ser Yee Lee

    (Duke-NUS Medical School
    National Cancer Centre
    Singapore General Hospital)

  • Peng Chung Cheow

    (Duke-NUS Medical School
    National Cancer Centre
    Singapore General Hospital)

  • Han Chong Toh

    (Duke-NUS Medical School
    National Cancer Centre)

  • Florent Ginhoux

    (Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre
    Singapore Immunology Network (SIgN), A*STAR)

  • Shridhar Iyer

    (University Surgical Cluster, National University Health System)

  • Alfred W. C. Kow

    (University Surgical Cluster, National University Health System)

  • Yock Young Dan

    (National University Hospital Singapore)

  • Alexander Chung

    (Duke-NUS Medical School
    National Cancer Centre
    Singapore General Hospital)

  • Glen K. Bonney

    (University Surgical Cluster, National University Health System)

  • Brian K. P. Goh

    (Duke-NUS Medical School
    National Cancer Centre
    Singapore General Hospital)

  • Salvatore Albani

    (Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre)

  • Pierce K. H. Chow

    (Duke-NUS Medical School
    National Cancer Centre
    Singapore General Hospital)

  • Weiwei Zhai

    (Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)
    Institute of Zoology, Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Valerie Chew

    (Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre)

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.

Suggested Citation

  • Phuong H. D. Nguyen & Siming Ma & Cheryl Z. J. Phua & Neslihan A. Kaya & Hannah L. H. Lai & Chun Jye Lim & Jia Qi Lim & Martin Wasser & Liyun Lai & Wai Leong Tam & Tony K. H. Lim & Wei Keat Wan & Trac, 2021. "Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20171-7
    DOI: 10.1038/s41467-020-20171-7
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