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Tumor biology and immune infiltration define primary liver cancer subsets linked to overall survival after immunotherapy

  1. Author:
    Budhu, Anuradha
    Pehrsson,Erica
    He, Aiwu
    Goyal, Lipika
    Kelley, Robin Kate
    Dang, Hien
    Xie, Changqing
    Monge, Cecilia
    Tandon, Mayank
    Ma, Lichun
    Revsine, Mahler
    Kuhlman, Laura
    Zhang, Karen
    Baiev, Islam
    Lamm, Ryan
    Patel, Keyur
    Kleiner, David E
    Hewitt, Stephen M
    Tran,Bao
    Shetty,Jyoti
    Wu,Xiaolin
    Zhao,Yongmei
    Shen,Tsai-Wei
    Choudhari,Sulbha
    Kriga,Yuliya
    Ylaya, Kris
    Warner,Andrew
    Edmondson,Elijah
    Forgues, Marshonna
    Greten, Tim F
    Wang, Xin Wei

  2. Author Address

    Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; CCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA., Department of Medical Oncology, Mass General Cancer Center, Harvard Medical School, Boston, MA 02114, USA., Department of Medicine (Hematology/Oncology), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94143, USA., Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA; Sidney Kimmel Cancer Center, Philadelphia, PA 19107, USA., Gastrointestinal Malignancies Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 21701, USA., Sequencing Facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Genomics Technology Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Molecular Histopathology Laboratory, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Gastrointestinal Malignancies Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tim.greten@nih.gov., Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: xw3u@nih.gov.,
    1. Year: 2023
    2. Date: May 16
    3. Epub Date: 2023 05 16
  2. Journal: Cell Reports. Medicine
    1. 4
    2. 6
    3. Pages: 101052
  4. Type of Article: Article
  5. Article Number: 101052
  1. Abstract:

    Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field. In a retrospective arm of the National Cancer Institute Cancers of the Liver: Accelerating Research of Immunotherapy by a Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and cholangiocarcinoma patients prior to and following immune checkpoint inhibitor treatment. Using supervised and unsupervised approaches, we identify stable molecular subtypes linked to overall survival and distinguished by two axes of aggressive tumor biology and microenvironmental features. Moreover, molecular responses to immune checkpoint inhibitor treatment differ between subtypes. Thus, patients with heterogeneous liver cancer may be stratified by molecular status indicative of treatment response to immune checkpoint inhibitors. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.xcrm.2023.101052
  3. PMID: 37224815
  4. View record in Web of Science®
  5. WOS: 001037326500001
  6. PII : S2666-3791(23)00166-0

Library Notes

  1. Fiscal Year: FY2022-2023
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