Resistance to anticancer vaccination effect is controlled by a cancer cell-autonomous phenotype that disrupts immunogenic phagocytic removal

Oncotarget
Abhishek D GargPatrizia Agostinis

Abstract

Immunogenic cell death (ICD) is a well-established instigator of 'anti-cancer vaccination-effect (AVE)'. ICD has shown considerable preclinical promise, yet there remain subset of cancer patients that fail to respond to clinically-applied ICD inducers. Non-responsiveness to ICD inducers could be explained by the existence of cancer cell-autonomous, anti-AVE resistance mechanisms. However such resistance mechanisms remain poorly investigated. In this study, we have characterized for the first time, a naturally-occurring preclinical cancer model (AY27) that exhibits intrinsic anti-AVE resistance despite treatment with ICD inducers like mitoxantrone or hypericin-photodynamic therapy. Further mechanistic analysis revealed that this anti-AVE resistance was associated with a defect in exposing the important 'eat me' danger signal, surface-calreticulin (ecto-CRT/CALR). In an ICD setting, this defective ecto-CRT further correlated with severely reduced phagocytic clearance of AY27 cells as well as the failure of these cells to activate AVE. Defective ecto-CRT in response to ICD induction was a result of low endogenous CRT protein levels (i.e. CRTlow-phenotype) in AY27 cells. Exogenous reconstitution of ecto-rCRT (recombinant-CRT) impro...Continue Reading

References

Oct 27, 1998·International Journal of Radiation Oncology, Biology, Physics·M P Mac ManusR T Hoppe
Sep 3, 1999·Breast Cancer Research and Treatment·L PusztaiG N Hortobagyi
Sep 25, 2003·International Journal of Cancer. Journal International Du Cancer·Appolinary A R KamuhabwaPeter A M de Witte
Feb 12, 2004·Bioinformatics·M J L de HoonS Miyano
Apr 8, 2004·Neoplasia : an International Journal for Oncology Research·Daniel R RhodesArul M Chinnaiyan
Jun 8, 2004·Bioinformatics·Alok J Saldanha
Jan 26, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·W M HsuW J Chen
Feb 4, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Esther BuytaertPatrizia Agostinis
Dec 26, 2006·Nature Medicine·Michel ObeidGuido Kroemer
Mar 16, 2007·Neoplasia : an International Journal for Oncology Research·Daniel R RhodesArul M Chinnaiyan
Jun 30, 2007·Nature Reviews. Drug Discovery·Elizabeth IornsAlan Ashworth
May 10, 2008·Cell Death and Differentiation·T PanaretakisG Kroemer
Oct 7, 2008·Biophysical Journal·Jonathan LamVolkmar Heinrich
Jan 24, 2009·The EMBO Journal·Theocharis PanaretakisGuido Kroemer
Apr 2, 2010·Seminars in Immunology·Cheryl Lai-Lai ChiangGeorge Coukos
May 19, 2010·World Journal of Gastroenterology : WJG·Rui-Qing PengXiao-Shi Zhang
Jun 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Douglas E JamesP Edward Purdue
Sep 8, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Giorgio GiannattasioBarbara Balestrieri
Sep 14, 2010·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Zin-Mar LwinBoon-Huat Bay
Sep 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sandeepa Dey, Hiroaki Matsunami
Nov 3, 2011·Nature Communications·Sudesh Pawaria, Robert J Binder
Nov 30, 2011·Photodiagnosis and Photodynamic Therapy·Renata SanovicBarbara Krammer
Dec 24, 2011·Cancer Immunology, Immunotherapy : CII·Abhishek D GargPatrizia Agostinis
Mar 8, 2012·Nature Medicine·Metamia CiampricottiKarin E de Visser
Mar 21, 2012·The American Journal of Pathology·Masanori HisaokaMitsuhiro Nakamoto
Jun 19, 2012·Cell Death and Differentiation·T VerfaillieP Agostinis
Sep 29, 2012·Science·Laura SenovillaGuido Kroemer
Oct 23, 2012·Molecular Biology of the Cell·Chiye SakuraiKiyotaka Hatsuzawa
Nov 16, 2012·Nature Reviews. Cancer·Dmitri V KryskoPeter Vandenabeele
Nov 20, 2012·Annual Review of Immunology·Guido KroemerLaurence Zitvogel
Feb 9, 2013·Cytokine & Growth Factor Reviews·Aleksandra M DudekPatrizia Agostinis
May 21, 2013·Cell Death and Differentiation·A D GargP Agostinis
Jul 31, 2013·Immunity·Karolina Palucka, Jacques Banchereau
Aug 1, 2013·BioFactors·Abhishek D GargPatrizia Agostinis
Aug 7, 2013·Biochemical and Biophysical Research Communications·Tom VerfailliePatrizia Agostinis

❮ Previous
Next ❯

Citations

Feb 20, 2016·Expert Review of Molecular Diagnostics·Ben Davidson
Apr 12, 2016·Frontiers in Immunology·Abhishek D Garg, Patrizia Agostinis
Dec 7, 2017·Oncoimmunology·Abhishek D GargLorenzo Galluzzi
Mar 27, 2020·Journal for Immunotherapy of Cancer·Lorenzo GalluzziFrancesco M Marincola
Sep 19, 2020·Molecular & Cellular Oncology·Juliette HumeauGuido Kroemer
Dec 5, 2015·Frontiers in Immunology·Abhishek D GargPatrizia Agostinis
Oct 14, 2017·Immunological Reviews·Abhishek D Garg, Patrizia Agostinis
Apr 8, 2019·Archives of Pharmacal Research·Marc Diederich
Apr 4, 2019·Frontiers in Oncology·Maxim ShevtsovAtsushi Shibata
Feb 13, 2016·Biological Chemistry·Alexander R van VlietPatrizia Agostinis
Aug 17, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·W G LandA Linkermann
May 21, 2016·Frontiers in Plant Science·Zuzana JendželovskáPeter Fedoročko
Feb 1, 2018·Therapeutic Advances in Medical Oncology·Thomas WalleFernando Lecanda
May 1, 2018·Oncotarget·Erminia RomanoPatrizia Agostinis
Nov 1, 2016·Nature Reviews. Immunology·Lorenzo GalluzziGuido Kroemer
Aug 25, 2015·Frontiers in Immunology·Jitka FucikovaRadek Spisek
Apr 19, 2016·Oncogene·C HernandezR F Schwabe
Feb 22, 2018·Physiological Reviews·Maysa SarhanAndreas Linkermann
Jan 25, 2018·Cell Death and Differentiation·Lorenzo GalluzziGuido Kroemer
Aug 16, 2017·Oncoimmunology·Abhishek D GargLorenzo Galluzzi
May 2, 2019·Frontiers in Cell and Developmental Biology·Alfonso Serrano-Del ValleIsabel Marzo
Aug 1, 2020·Cell Research·Jitka FucikovaLorenzo Galluzzi
Mar 30, 2021·Advanced Drug Delivery Reviews·Mina MehannyGregor Fuhrmann
May 1, 2021·Cells·Rianne D W VaesDirk De Ruysscher
Jan 8, 2019·Biochemical Pharmacology·Flavia RadognaMarc Diederich
Feb 1, 2020·Oncoimmunology·Isaure VanmeerbeekAbhishek D Garg
May 28, 2019·Advanced Drug Delivery Reviews·Yoosoo YangIn-San Kim

❮ Previous
Next ❯

Methods Mentioned

BETA
FACS
transfection

Software Mentioned

TreeView
GraphPad QuickCalcs
KMPlotter
Cluster
Prism
Oncomine

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.