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dc.contributor.authorHo W.J.
dc.contributor.authorDanilova L.
dc.contributor.authorSztein M.B.
dc.date.accessioned2020-05-01T19:06:47Z
dc.date.available2020-05-01T19:06:47Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85083712084&doi=10.1136%2fjitc-2019-000394&partnerID=40&md5=5cac36e44e83ed4b9b645ead63ff6f06
dc.identifier.urihttp://hdl.handle.net/10713/12684
dc.description.abstractBackground 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.en_US
dc.description.urihttps://doi.org/10.1136/jitc-2019-000394en_US
dc.language.isoen_USen_US
dc.publisherBMJ Publishing Groupen_US
dc.relation.ispartofJournal for ImmunoTherapy of Cancer
dc.subjectimmunologyen_US
dc.subjectliver diseaseen_US
dc.subjectmeta-analysisen_US
dc.subjectoncologyen_US
dc.titleViral status, immune microenvironment and immunological response to checkpoint inhibitors in hepatocellular carcinomaen_US
dc.typeArticleen_US
dc.identifier.doi10.1136/jitc-2019-000394
dc.identifier.pmid32303615


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