Immunological mechanisms of the antitumor effects of supplemental oxygenation

Science Translational Medicine
Stephen M HatfieldMichail V Sitkovsky

Abstract

Antitumor T cells either avoid or are inhibited in hypoxic and extracellular adenosine-rich tumor microenvironments (TMEs) by A2A adenosine receptors. This may limit further advances in cancer immunotherapy. There is a need for readily available and safe treatments that weaken the hypoxia-A2-adenosinergic immunosuppression in the TME. Recently, we reported that respiratory hyperoxia decreases intratumoral hypoxia and concentrations of extracellular adenosine. We show that it also reverses the hypoxia-adenosinergic immunosuppression in the TME. This, in turn, stimulates (i) enhanced intratumoral infiltration and reduced inhibition of endogenously developed or adoptively transfered tumor-reactive CD8 T cells, (ii) increased proinflammatory cytokines and decreased immunosuppressive molecules, such as transforming growth factor-β (TGF-β), (iii) weakened immunosuppression by regulatory T cells, and (iv) improved lung tumor regression and long-term survival in mice. Respiratory hyperoxia also promoted the regression of spontaneous metastasis from orthotopically grown breast tumors. These effects are entirely T cell- and natural killer cell-dependent, thereby justifying the testing of supplemental oxygen as an immunological coadjuvant...Continue Reading

References

Aug 1, 1997·Circulation Research·U K DeckingJ Schrader
Nov 5, 1997·The Journal of Biological Chemistry·M KoshibaM V Sitkovsky
Feb 9, 2000·American Journal of Physiology. Heart and Circulatory Physiology·H OoiP McLoughlin
Nov 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J KjaergaardS Shu
Jul 17, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jørgen KjaergaardSuyu Shu
Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tatiana RaskovalovaElieser Gorelik
Aug 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Akio OhtaMichail Sitkovsky
Nov 21, 2007·Nature·Catherine M KoebelRobert D Schreiber
Mar 21, 2008·Nature Reviews. Cancer·Steven A RosenbergMark E Dudley
May 27, 2008·Nature Reviews. Cancer·Mark W DewhirstBenjamin Moeller
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michail V SitkovskyAkio Ohta
Oct 11, 2008·Science·Kajsa WingShimon Sakaguchi
Nov 5, 2008·Cancer Biology & Therapy·Jie Wang, Jing Yi
Feb 19, 2009·Cancer Research·Taylor H SchreiberEckhard R Podack
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·John StaggMark J Smyth
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Jun 12, 2010·Immunological Reviews·Marine Champsaur, Lewis L Lanier
Sep 30, 2010·The Journal of Experimental Medicine·Cesar A CorzoDmitry I Gabrilovich
Apr 13, 2011·Purinergic Signalling·Beat M KünzliSimon C Robson
Oct 25, 2011·Nature Reviews. Cancer·Padmanee SharmaJames P Allison
Nov 26, 2011·Cancer Immunology, Immunotherapy : CII·Adam T WaickmanJonathan D Powell
Dec 24, 2011·Nature·Ira MellmanGlenn Dranoff
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Jul 31, 2012·American Journal of Respiratory Cell and Molecular Biology·Eric KratzerAnna A Birukova
Dec 14, 2012·The New England Journal of Medicine·Holger K EltzschigSimon C Robson
Dec 29, 2012·Respiratory Care·Richard H Kallet, Michael A Matthay
Jan 10, 2013·Annual Review of Immunology·David H RauletHeiyoun Jung
Jun 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sherene LoiJohn Stagg
Aug 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Paul A BeavisPhillip K Darcy
May 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Pallavi ChaturvediGregg L Semenza
Jul 6, 2014·Cancer Immunology Research·Michail V SitkovskyAkio Ohta
Jul 19, 2014·Cancer Discovery·Arabella YoungMark J Smyth
Aug 15, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Stephen M HatfieldMichail Sitkovsky
Sep 12, 2014·British Journal of Cancer·J NaidooJ D Wolchok

❮ Previous
Next ❯

Citations

Nov 26, 2015·Nature Reviews. Clinical Oncology·Mark J SmythMichele W L Teng
Jan 26, 2016·Immunotherapy·David AllardJohn Stagg
Feb 24, 2016·Human Immunology·Petya Apostolova, Robert Zeiser
Oct 30, 2015·Proceedings of the National Academy of Sciences of the United States of America·Huimin ZhangGregg L Semenza
Dec 8, 2015·The Journal of Clinical Investigation·Jessica L BowserRussell R Broaddus
Nov 14, 2015·Molecular Oncology·Lynsey M Whilding, John Maher
Mar 11, 2016·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·Peter Vaupel, Gabriele Multhoff
Jun 16, 2015·Pharmacology & Therapeutics·Dietmar W Siemann, Michael R Horsman
Apr 12, 2016·Frontiers in Immunology·Akio Ohta
Nov 22, 2015·American Journal of Reproductive Immunology : AJRI·Fan WuWang-Ming Xu
Oct 10, 2015·Oncoimmunology·Paul A BeavisPhillip K Darcy
Apr 29, 2016·Science·Erinn B Rankin, Amato J Giaccia
Aug 1, 2015·Nature Reviews. Drug Discovery·Kathleen M MahoneyGordon J Freeman
May 5, 2016·Trends in Immunology·Davide FerrariHolger K Eltzschig
Jun 21, 2016·Oncogene·F Di Virgilio, E Adinolfi
Aug 2, 2016·Current Opinion in Pharmacology·Francesco Di Virgilio, Paolo Pinton
Dec 9, 2016·Vaccines·Nicole E Scharping, Greg M Delgoffe
Jan 14, 2017·Expert Opinion on Therapeutic Targets·Anna Rita CantelmoPeter Carmeliet
Feb 9, 2017·Immunology and Cell Biology·David AllardJohn Stagg
Mar 5, 2017·Immunological Reviews·Bertrand AllardJohn Stagg
Jan 21, 2017·Journal for Immunotherapy of Cancer·Laura Conforti
Jul 4, 2017·Nature Reviews. Immunology·Manan M MehtaNavdeep S Chandel
Aug 26, 2017·International Journal of Molecular Sciences·Jae-Young Kim, Joo-Yong Lee
Feb 2, 2018·High Altitude Medicine & Biology·Markus Thiersch, Erik R Swenson
Apr 18, 2018·The Journal of Clinical Investigation·Xichen ZhengYuhui Huang
Oct 24, 2017·Nature Reviews. Cancer·Dipti VijayanMark J Smyth
Sep 26, 2017·Nature Reviews. Immunology·Glenn R BantugChristoph Hess
May 31, 2018·International Immunology·Akio Ohta
May 29, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jorgen KjaergaardMichail Sitkovsky
Jan 24, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica L BowserHolger K Eltzschig
Sep 7, 2018·The Journal of Clinical Investigation·Priyamvada JayaprakashMichael A Curran
Jan 27, 2018·Cell Death & Disease·Marco B SchaafPatrizia Agostinis
Jun 18, 2017·The European Respiratory Journal·Enrique Hernández-JiménezEduardo López-Collazo
Jan 26, 2018·Proceedings of the National Academy of Sciences of the United States of America·Debangshu SamantaGregg L Semenza
Mar 1, 2016·Nature Reviews. Immunology·Caglar Cekic, Joel Linden

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Cancer Vaccines

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

Cancer Metabolism: Therapeutic Targets

Targeting the mechanisms by which cancer cells acquire energy for metabolic needs is a therapeutic target. Discover the latest research on cancer metabolism and therapeutic targets.

Related Papers

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Stephen M HatfieldMichail V Sitkovsky
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Michail V SitkovskyAkio Ohta
Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Michail V Sitkovsky, Akio Ohta
© 2022 Meta ULC. All rights reserved