Augmentation of IFN-γ+ CD8+ T cell responses correlates with survival of HCC patients on sorafenib therapy

JCI Insight
Suresh Gopi KalathilYasmin Thanavala

Abstract

BACKGROUNDSorafenib has been shown to reduce the extent of immunosuppression in patients with hepatocellular carcinoma (HCC). The rationale of this investigation was to identify biomarkers that can predict treatment efficacy of sorafenib in HCC patients and to unravel the mechanism by which sorafenib impedes immune suppression mediated by distinct immunosuppressive cell subsets.METHODSWith informed consent, blood samples were collected from 30 patients with advanced HCC, at baseline and 2 time points after initiation of sorafenib treatment. The frequency of PD-1+ T cells, ERK2 phosphorylation on flt-3+ Tregs and MDSCs, and T effector cell function were quantified by using flow cytometry.RESULTSElevated levels of CD8+Ki67+ T cells producing IFN-γ were associated with improved progression-free survival and overall survival (OS). High frequencies of these T cells were correlated with significantly reduced risk of death over time. Patients with an increased pretreatment T effector/Treg ratio showed significant improvement in OS. ERK+flt-3+ Tregs and MDSCs were significantly decreased after sorafenib therapy. Increased numbers of baseline flt-3+p-ERK+ MDSCs were associated with survival benefit of patients.CONCLUSIONA high baseline ...Continue Reading

References

Aug 16, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ghassan K Abou-AlfaLeonard B Saltz
Jan 16, 2007·Nature·Marc A GavinAlexander Y Rudensky
Dec 9, 2010·The Oncologist·Arun J SanyalRiccardo Lencioni
Feb 16, 2011·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mengde CaoChen Liu
Aug 22, 2012·International Journal of Cancer. Journal International Du Cancer·Yung-Chang LinChun-Yen Lin
Oct 26, 2012·Alimentary Pharmacology & Therapeutics·R CabreraD R Nelson
Nov 6, 2012·European Journal of Immunology·Oliver KleinJonathan Cebon
Dec 12, 2012·Cancer Immunology, Immunotherapy : CII·Roniel CabreraDavid R Nelson
Jul 3, 2013·International Journal of Cancer. Journal International Du Cancer·Mei-Ling ChenAnn-Lii Cheng
May 16, 2014·American Journal of Respiratory and Critical Care Medicine·Suresh Gopi KalathilYasmin Thanavala
May 20, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hashem B El-Serag, Fasiha Kanwal
Aug 2, 2014·Oncoimmunology·Anna KreutzmanSatu Mustjoki
Jan 21, 2015·The Journal of Experimental Medicine·Thibault VoronMagali Terme
Mar 13, 2015·Molecular Cancer Therapeutics·Lisa ChristianssonUlla Olsson-Strömberg
Oct 21, 2015·Nature Reviews. Gastroenterology & Hepatology·Jesús PrietoBruno Sangro
Feb 26, 2016·Cancer Immunology, Immunotherapy : CII·Suresh Gopi Kalathil, Yasmin Thanavala
May 10, 2016·Nature Reviews. Disease Primers·Josep M LlovetGregory Gores
Sep 9, 2017·Cell·Yenkel Grinberg-BleyerSankar Ghosh
Sep 12, 2017·Nature Immunology·Ho-Keun KwonChristophe Benoist
Dec 20, 2017·Oncology·Masatoshi Kudo
Jan 9, 2018·Lancet·Alejandro FornerJordi Bruix

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Citations

Feb 11, 2020·British Journal of Cancer·Christos FountzilasRenuka Iyer
Jan 11, 2020·Frontiers in Oncology·Maria Carolina Mangini PradoCarlos Eduardo Fonseca-Alves
Apr 25, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Erin BresnahanAmaia Lujambio
Jan 14, 2021·Cancer Immunology, Immunotherapy : CII·Minhui ChenKaterina V Gurova
Nov 19, 2020·Cellular & Molecular Immunology·Yong HeBin Gao
Jan 15, 2021·Cellular Immunology·Suresh Gopi Kalathil, Yasmin Thanavala
Dec 18, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David J PinatoLorenza Rimassa
Apr 16, 2021·Frontiers in Immunology·Morgane BourhisMagali Terme
May 7, 2021·Frontiers in Immunology·Yara O AghabiZania Stamataki
Jun 23, 2021·Nature Reviews. Immunology·Angela M GocherDario A A Vignali
Sep 2, 2021·Computer Methods and Programs in Biomedicine·Alan D Hutson
Sep 9, 2021·The Journal of Experimental Medicine·Juliette PailletJonathan G Pol

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Methods Mentioned

BETA
flow cytometry
blood draw
biopsies
xenograft
density gradient centrifugation

Clinical Trials Mentioned

NCT02072486

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