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    Viral status, immune microenvironment and immunological response to checkpoint inhibitors in hepatocellular carcinoma

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    Author
    Ho W.J.
    Danilova L.
    Sztein M.B.
    Date
    2020
    Journal
    Journal for ImmunoTherapy of Cancer
    Publisher
    BMJ Publishing Group
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1136/jitc-2019-000394
    Abstract
    Background and aims Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have clinical activity in hepatocellular carcinoma (HCC), but only a subset of patients respond to these therapies, highlighting a need for novel biomarkers to improve clinical benefit. HCC usually occurs in the setting of liver cirrhosis from chronic hepatitis B or C viral infection, but the effects of viral status on the tumor immune microenvironment and clinical responses to ICIs in HCC remains unclear. Methods We conducted a meta-analysis to estimate the objective response rates for PD-1/PD-L1 inhibitors in virally-infected and uninfected patients, and examined the effects of viral etiology on the tumor microenvironment using data from The Cancer Genome Atlas, as well as peripheral blood responses using an independent cohort of patients studied by mass cytometry (cytometry by time-of-flight (CyTOF)). Results Meta-analysis comparing objective response rates (ORR) between virally-infected and uninfected patients showed no clinically meaningful difference (absolute difference of ORR in virally-infected vs uninfected=-1.4%, 95% CI: -13.5% to 10.6%). There was no relationship between viral etiology on features of the tumor immune microenvironment that are known to modulate responses to PD-1/PD-L1 inhibitors, and the tumor mutational burden was similar between virally-infected and uninfected HCC. RNA sequencing of tissue-resident T cell and B cell repertoires similarly showed no effect of viral status on their diversity. CyTOF analysis of peripheral blood specimens further demonstrated similar expression of immune-related markers in response to PD-1 inhibitor therapy in virally-infected and uninfected HCC. Conclusion There is no significant effect of viral etiology on the tumor immune microenvironment in HCC, and viral status should not be used as a criterion to select patients for PD-1/PD-L1 therapy. Copyright Author(s) (or their employer(s)) 2020.
    Keyword
    immunology
    liver disease
    meta-analysis
    oncology
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083712084&doi=10.1136%2fjitc-2019-000394&partnerID=40&md5=5cac36e44e83ed4b9b645ead63ff6f06; http://hdl.handle.net/10713/12684
    ae974a485f413a2113503eed53cd6c53
    10.1136/jitc-2019-000394
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    UMB Open Access Articles 2020

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