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Trajectory of immune evasion and cancer progression in hepatocellular carcinoma

Author

Listed:
  • Phuong H. D. Nguyen

    (SingHealth-DukeNUS Academic Medical Centre)

  • Martin Wasser

    (SingHealth-DukeNUS Academic Medical Centre
    Duke-Nus Medical School)

  • Chong Teik Tan

    (National University of Singapore)

  • Chun Jye Lim

    (SingHealth-DukeNUS Academic Medical Centre)

  • Hannah L. H. Lai

    (Agency for Science, Technology and Research (A*STAR))

  • Justine Jia Wen Seow

    (Agency for Science, Technology and Research (A*STAR))

  • Ramanuj DasGupta

    (Agency for Science, Technology and Research (A*STAR))

  • Cheryl Z. J. Phua

    (Agency for Science, Technology and Research (A*STAR))

  • Siming Ma

    (Agency for Science, Technology and Research (A*STAR))

  • Jicheng Yang

    (Duke-Nus Medical School)

  • Sheena D/O Suthen

    (SingHealth-DukeNUS Academic Medical Centre)

  • Wai Leong Tam

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

  • Tony K. H. Lim

    (Duke-Nus Medical School
    Singapore General Hospital)

  • Joe Yeong

    (Duke-Nus Medical School
    Singapore General Hospital
    Technology and Research (A*STAR))

  • Wei Qiang Leow

    (Duke-Nus Medical School
    Singapore General Hospital)

  • Yin Huei Pang

    (National University Hospital)

  • Gwyneth Soon

    (National University Hospital)

  • Tracy Jiezhen Loh

    (Singapore General Hospital)

  • Wei Keat Wan

    (Singapore General Hospital)

  • Chung Yip Chan

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

  • Peng Chung Cheow

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

  • Han Chong Toh

    (Duke-Nus Medical School
    National Cancer Centre Singapore)

  • Alfred Kow

    (University Surgical Cluster, National University Health System)

  • Yock Young Dan

    (National University of Singapore)

  • Juinn Huar Kam

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

  • Shridhar Iyer

    (University Surgical Cluster, National University Health System)

  • Krishnakumar Madhavan

    (University Surgical Cluster, National University Health System)

  • Alexander Chung

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

  • Glenn K. Bonney

    (University Surgical Cluster, National University Health System)

  • Brian K. P. Goh

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

  • Naiyang Fu

    (Duke-Nus Medical School)

  • Victor C. Yu

    (National University of Singapore)

  • Weiwei Zhai

    (Agency for Science, Technology and Research (A*STAR)
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Salvatore Albani

    (SingHealth-DukeNUS Academic Medical Centre
    Duke-Nus Medical School)

  • Pierce K. H. Chow

    (Singapore General Hospital and National Cancer Centre Singapore
    SingHealth Duke-NUS Academic Medical Centre (AMC))

  • Valerie Chew

    (SingHealth-DukeNUS Academic Medical Centre
    Duke-Nus Medical School)

Abstract

Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours. Corresponding transcriptomic modification occur in the genes related to antigen presentation, immune responses, and chemotaxis. The progressive immune evasion is validated in a murine model of HCC. Our results show evidence of ongoing tumour-immune co-evolution during HCC progression and offer insights into potential interventions to reverse, prevent or limit the progression of the disease.

Suggested Citation

  • Phuong H. D. Nguyen & Martin Wasser & Chong Teik Tan & Chun Jye Lim & Hannah L. H. Lai & Justine Jia Wen Seow & Ramanuj DasGupta & Cheryl Z. J. Phua & Siming Ma & Jicheng Yang & Sheena D/O Suthen & Wa, 2022. "Trajectory of immune evasion and cancer progression in hepatocellular carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29122-w
    DOI: 10.1038/s41467-022-29122-w
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    References listed on IDEAS

    as
    1. Rachel Rosenthal & Elizabeth Larose Cadieux & Roberto Salgado & Maise Al Bakir & David A. Moore & Crispin T. Hiley & Tom Lund & Miljana Tanić & James L. Reading & Kroopa Joshi & Jake Y. Henry & Ehsan , 2019. "Neoantigen-directed immune escape in lung cancer evolution," Nature, Nature, vol. 567(7749), pages 479-485, March.
    2. Céline Mascaux & Mihaela Angelova & Angela Vasaturo & Jennifer Beane & Kahkeshan Hijazi & Geraldine Anthoine & Bénédicte Buttard & Françoise Rothe & Karen Willard-Gallo & Annick Haller & Vincent Ninan, 2019. "Immune evasion before tumour invasion in early lung squamous carcinogenesis," Nature, Nature, vol. 571(7766), pages 570-575, July.
    Full references (including those not matched with items on IDEAS)

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