Preclinical efficacy of immune-checkpoint monotherapy does not recapitulate corresponding biomarkers-based clinical predictions in glioblastoma

Oncoimmunology
Abhishek D GargPatrizia Agostinis

Abstract

Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression. Based on these analyses, we found that predictive biomarkers of ICI responsiveness exhibited inconsistent patterns in GBM patients, i.e., they either predicted ICI resistance (as compared with typical ICI-responsive cancer-types like melanoma, lung cancer or bladder cancer) or susceptibility to therapeutic targeting of CTLA4 or IDO1. On the other hand, our c...Continue Reading

References

Sep 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jonathan R PollackPatrick O Brown
Feb 12, 2004·Bioinformatics·M J L de HoonS Miyano
Jun 8, 2004·Bioinformatics·Alok J Saldanha
Apr 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Peter E FecciJohn H Sampson
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Feb 12, 2009·Molecular Cancer Research : MCR·Subha MadhavanKenneth Buetow
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Jan 26, 2013·European Journal of Immunology·Isabel VogelJan L Ceuppens
Mar 7, 2013·International Journal of Radiation Oncology, Biology, Physics·Jing ZengMichael Lim
May 21, 2013·Cell Death and Differentiation·A D GargP Agostinis
Aug 10, 2013·International Journal of Cancer. Journal International Du Cancer·Tina VerschuereSteven De Vleeschouwer
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
Sep 28, 2013·Nature Genetics·UNKNOWN Cancer Genome Atlas Research NetworkJoshua M Stuart
Oct 15, 2013·Cell·Cameron W BrennanUNKNOWN TCGA Research Network
Oct 29, 2013·FEBS Letters·Chrisann Kyi, Michael A Postow
Nov 28, 2013·The Journal of Experimental Medicine·Johannes Vom BergBurkhard Becher
Apr 3, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Derek A WainwrightMaciej S Lesniak
May 30, 2014·The Lancet Oncology·Sébastien AnguilleZwi N Berneman
Sep 12, 2014·International Journal of Cancer. Journal International Du Cancer·Carolien A KoksStefaan W Van Gool
Dec 19, 2014·BMC Cancer·Chirayu Pankaj Goswami, Harikrishna Nakshatri
Dec 30, 2014·British Journal of Neurosurgery·Stavros PolyzoidisKeyoumars Ashkan
Mar 11, 2015·Nature·Christina Twyman-Saint VictorAndy J Minn
Apr 4, 2015·Science·Padmanee Sharma, James P Allison
Apr 4, 2015·Science·Ton N Schumacher, Robert D Schreiber
Apr 22, 2015·The New England Journal of Medicine·Caroline RobertUNKNOWN KEYNOTE-006 investigators
Jul 16, 2015·International Journal of Cancer. Journal International Du Cancer·Dimitrios MathiosMichael Lim
Jul 21, 2015·Nature Medicine·Andrew J GentlesAsh A Alizadeh
Aug 12, 2015·Nature Reviews. Neurology·Matthias PreusserJohn H Sampson
Sep 12, 2015·Science·Eliezer M Van AllenLevi A Garraway
Nov 8, 2015·Cancer Immunology Research·David A ReardonGordon J Freeman
Dec 5, 2015·Frontiers in Immunology·Abhishek D GargPatrizia Agostinis
Mar 24, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric BouffetUri Tabori
May 7, 2016·Science·Christian U BlankTon N Schumacher

❮ Previous
Next ❯

Citations

Feb 16, 2018·Frontiers in Immunology·Lilla HornyákLóránt Székvölgyi
Dec 7, 2017·Oncoimmunology·Abhishek D GargLorenzo Galluzzi
Jan 27, 2018·Cell Death & Disease·Marco B SchaafPatrizia Agostinis
Feb 8, 2019·Journal of Experimental & Clinical Cancer Research : CR·Shuang FengBin Li
Feb 7, 2020·Expert Opinion on Biological Therapy·Steven H ShenJohn H Sampson
May 14, 2020·Expert Opinion on Investigational Drugs·Maria B Garcia-FabianiMaria G Castro
Aug 6, 2020·Cells·Jenny SprootenAbhishek D Garg
Aug 16, 2019·Physiological Reviews·Carla Riera-DomingoMassimiliano Mazzone
Oct 14, 2017·Immunological Reviews·Abhishek D Garg, Patrizia Agostinis
Dec 14, 2017·International Journal of Genomics·Barbara BanelliMassimo Romani
Mar 16, 2019·BMC Medical Genomics·Anna V KudryavtsevaAnastasiya V Snezhkina
Mar 3, 2020·Frontiers in Immunology·Malte Mohme, Marian Christoph Neidert
Jan 9, 2020·Cancer Cell International·Fangkun LiuZhixiong Liu
Feb 1, 2020·Oncoimmunology·Isaure VanmeerbeekAbhishek D Garg
May 28, 2020·Journal for Immunotherapy of Cancer·Di ChenLiangfu Zhou
Mar 7, 2020·Frontiers in Immunology·Rachael M ZemekW Joost Lesterhuis
Aug 16, 2017·Oncoimmunology·Abhishek D GargLorenzo Galluzzi
Dec 14, 2018·Oncoimmunology·Jonathan G PolLorenzo Galluzzi
May 10, 2018·Hepatology International·Antonio Riva, Shilpa Chokshi
Oct 28, 2019·Oncoimmunology·Jenny SprootenAbhishek D Garg
Oct 30, 2020·International Reviews of Immunology·Fahimeh HeidariMahboobeh Razmkhah
Dec 21, 2021·International Journal of Immunopathology and Pharmacology·Shaoping ShenTianyi Liu

❮ Previous
Next ❯

Methods Mentioned

BETA
surgical resection
flow cytometry
xenograft

Clinical Trials Mentioned

NCT02085070
NCT02337491
NCT01952769
NCT01950195
NCT01703507
NCT02107755
NCT02097732
NCT02115139

Software Mentioned

Cluster
FlowJo
Project βstasis
PROGgeneV2
REMBRANDT
Graphpad Prism
TreeView
GraphPad QuickCalcs
βstasis
Project

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.