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

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; Tracy Loh; Wei Qiang Leow; Yin Huei Pang; Chung Yip Chan; Ser Yee Lee; Peng Chung Cheow; Han Chong Toh; Florent Ginhoux; Shridhar Iyer; Alfred W.C. Kow; Yock Young Dan; Alexander Chung; Brian K.P. Goh; Salvatore Albani; Pierce K.H. Chow; Weiwei Zhai; Valerie Chew

doi:10.1038/s41467-020-20171-7

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

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, Tracy Loh, Wei Qiang Leow, Yin Huei Pang, Chung Yip Chan, Ser Yee Lee, Peng Chung Cheow, Han Chong Toh, Florent GinhouxShridhar Iyer, Alfred W.C. Kow, Yock Young Dan, Alexander Chung, Brian K.P. Goh, Salvatore Albani, Pierce K.H. Chow, Weiwei Zhai, Valerie Chew

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

79 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Numéro d'article	227
journal	Nature Communications
Volume	12
Numéro de publication	1
Les DOIs	https://doi.org/10.1038/s41467-020-20171-7
état	Publié - 1 déc. 2021
Modification externe	Oui

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10.1038/s41467-020-20171-7

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Nguyen, P. H. D., Ma, S., Phua, C. Z. J., Kaya, N. A., Lai, H. L. H., Lim, C. J., Lim, J. Q., Wasser, M., Lai, L., Tam, W. L., Lim, T. K. H., Wan, W. K., Loh, T., Leow, W. Q., Pang, Y. H., Chan, C. Y., Lee, S. Y., Cheow, P. C., Toh, H. C., ... Chew, V. (2021). Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma. Nature Communications, 12(1), Article 227. https://doi.org/10.1038/s41467-020-20171-7

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title = "Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma",

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.",

author = "Nguyen, {Phuong H.D.} and Siming Ma and Phua, {Cheryl Z.J.} and Kaya, {Neslihan A.} and Lai, {Hannah L.H.} and Lim, {Chun Jye} and Lim, {Jia Qi} and Martin Wasser and Liyun Lai and Tam, {Wai Leong} and Lim, {Tony K.H.} and Wan, {Wei Keat} and Tracy Loh and Leow, {Wei Qiang} and Pang, {Yin Huei} and Chan, {Chung Yip} and Lee, {Ser Yee} and Cheow, {Peng Chung} and Toh, {Han Chong} and Florent Ginhoux and Shridhar Iyer and Kow, {Alfred W.C.} and {Young Dan}, Yock and Alexander Chung and Goh, {Brian K.P.} and Salvatore Albani and Chow, {Pierce K.H.} and Weiwei Zhai and Valerie Chew",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-020-20171-7",

language = "English",

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Nguyen, PHD, Ma, S, Phua, CZJ, Kaya, NA, Lai, HLH, Lim, CJ, Lim, JQ, Wasser, M, Lai, L, Tam, WL, Lim, TKH, Wan, WK, Loh, T, Leow, WQ, Pang, YH, Chan, CY, Lee, SY, Cheow, PC, Toh, HC, Ginhoux, F, Iyer, S, Kow, AWC, Young Dan, Y, Chung, A, Goh, BKP, Albani, S, Chow, PKH, Zhai, W & Chew, V 2021, 'Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma', Nature Communications, VOL. 12, Numéro 1, 227. https://doi.org/10.1038/s41467-020-20171-7

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T1 - Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma

AU - Nguyen, Phuong H.D.

AU - Ma, Siming

AU - Phua, Cheryl Z.J.

AU - Kaya, Neslihan A.

AU - Lai, Hannah L.H.

AU - Lim, Chun Jye

AU - Lim, Jia Qi

AU - Wasser, Martin

AU - Lai, Liyun

AU - Tam, Wai Leong

AU - Lim, Tony K.H.

AU - Wan, Wei Keat

AU - Loh, Tracy

AU - Leow, Wei Qiang

AU - Pang, Yin Huei

AU - Chan, Chung Yip

AU - Lee, Ser Yee

AU - Cheow, Peng Chung

AU - Toh, Han Chong

AU - Ginhoux, Florent

AU - Iyer, Shridhar

AU - Kow, Alfred W.C.

AU - Young Dan, Yock

AU - Chung, Alexander

AU - Goh, Brian K.P.

AU - Albani, Salvatore

AU - Chow, Pierce K.H.

AU - Zhai, Weiwei

AU - Chew, Valerie

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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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DO - 10.1038/s41467-020-20171-7

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SN - 2041-1723

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