Trajectory of immune evasion and cancer progression in hepatocellular carcinoma

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, Wai Leong Tam, Tony K. H. Lim, Joe Yeong, Wei Qiang Leow, Yin Huei Pang, Gwyneth Soon, Tracy Jiezhen Loh, Wei Keat Wan, Chung Yip Chan, Peng Chung Cheow, Han Chong Toh, Alfred Kow, Yock Young Dan, Juinn Huar Kam, Shridhar Iyer, Krishnakumar Madhavan, Alexander Chung, Glenn K. Bonney, Brian K. P. Goh, Naiyang Fu, Victor C. Yu, Weiwei Zhai, Salvatore Albani (), Pierce K. H. Chow () and Valerie Chew ()
Additional contact information
Phuong H. D. Nguyen: SingHealth-DukeNUS Academic Medical Centre
Martin Wasser: SingHealth-DukeNUS Academic Medical Centre
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)
Tony K. H. Lim: Duke-Nus Medical School
Joe Yeong: Duke-Nus Medical School
Wei Qiang Leow: Duke-Nus Medical School
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
Peng Chung Cheow: Duke-Nus Medical School
Han Chong Toh: Duke-Nus Medical School
Alfred Kow: University Surgical Cluster, National University Health System
Yock Young Dan: National University of Singapore
Juinn Huar Kam: Duke-Nus Medical School
Shridhar Iyer: University Surgical Cluster, National University Health System
Krishnakumar Madhavan: University Surgical Cluster, National University Health System
Alexander Chung: Duke-Nus Medical School
Glenn K. Bonney: University Surgical Cluster, National University Health System
Brian K. P. Goh: Duke-Nus Medical School
Naiyang Fu: Duke-Nus Medical School
Victor C. Yu: National University of Singapore
Weiwei Zhai: Agency for Science, Technology and Research (A*STAR)
Salvatore Albani: SingHealth-DukeNUS Academic Medical Centre
Pierce K. H. Chow: Singapore General Hospital and National Cancer Centre Singapore
Valerie Chew: SingHealth-DukeNUS Academic Medical Centre

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29122-w

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