Targeting macrophages in the tumour environment to enhance the efficacy of αOX40 therapy.

Immunology
Michael J GoughAndrew D Weinberg

Abstract

The treatment of high-grade tumours must consider a tumour environment dominated by cells that support cancer growth. In addition to directing angiogenesis and invasion, alternatively activated macrophages in the tumour provide protection from adaptive immunity and permit tumour growth. Agonist antibodies to the tumour necrosis factor receptor family member OX40 are an effective therapy for cancer in a range of murine models; however, as with many immune therapies, αOX40 therapy is less effective as the tumour grows and develops an immune suppressive environment. We demonstrate that αOX40 directly activates T cells and that this T-cell activation alters macrophage differentiation in the tumour environment. We demonstrate that macrophages in the tumour limit the efficacy of αOX40 therapy, and that combining αOX40 therapy with inhibitors of arginase significantly enhances survival of tumour-bearing mice. These data demonstrate that macrophages in the tumour environment limit the effectiveness of OX40-based immunotherapy, and combination therapies that target both the cell-mediated immune response and the suppressive tumour environment will be required for translation of effective immunotherapies to patients with established tumours.

References

Jun 1, 1974·Journal of the National Cancer Institute·R P ClevelandB Zbar
Aug 3, 1994·Journal of the National Cancer Institute·S A RosenbergD E White
Sep 14, 1994·Journal of Immunological Methods·I M CorralizaM Modolell
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A D WeinbergJ Shields
Nov 9, 2000·European Journal of Immunology·T YoshiokaK Okumura
Dec 12, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·D E EvansA D Weinberg
Oct 3, 2002·Nature Reviews. Immunology·Toby LawrenceDerek W Gilroy
Mar 8, 2003·Archives of Dermatological Research·Y MatsumuraY Miyachi
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuanqing LiuAnja B Geldhof
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paulo C RodriguezAugusto C Ochoa
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ikuo TakedaNaoto Ishii
May 12, 2004·Nature Reviews. Drug Discovery·Derek W GilroyAdriano G Rossi
Jul 20, 2004·European Journal of Immunology·Ralf BaumannHans-Uwe Simon
Nov 9, 2004·Trends in Immunology·Alberto MantovaniMassimo Locati
Apr 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael GoughRichard Vile
Sep 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aihua SongMichael Croft
Dec 22, 2005·Nature Immunology·Charles N Serhan, John Savill
Jan 21, 2006·Cancer Research·Claire E Lewis, Jeffrey W Pollard
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joseph R MaxwellAnthony T Vella
Sep 13, 2006·Cancer Metastasis Reviews·Alberto MantovaniAntonio Sica
Dec 22, 2006·European Journal of Immunology·Carl E RubyAndrew D Weinberg
Jan 11, 2007·Cancer Research·Dmitry I GabrilovichHans Schreiber
Feb 3, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Charles N SerhanJohn L Wallace
Apr 19, 2007·Cancer Research·Gerald KrystalMelisa Hamilton
May 4, 2007·The Journal of Clinical Investigation·Antonio Sica, Vincenzo Bronte
Nov 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·William L RedmondAndrew D Weinberg
Dec 29, 2007·The Journal of Pathology·C M Filippi, M G von Herrath
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carl E RubyAndrew D Weinberg
Mar 5, 2008·The Journal of Clinical Investigation·Bin ZhangHans Schreiber
Jul 3, 2008·Cancer Research·Michael J GoughAndrew D Weinberg
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie BenoitJean-Louis Mege
Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark KlingerNigel Killeen
Nov 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rodolfo D Vicetti MiguelKyle C McKenna

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Citations

May 9, 2013·Clinical & Developmental Immunology·Michael J GoughMarka Crittenden
Mar 22, 2016·Mediators of Inflammation·Michal A Rahat, Jivan Shakya
Dec 10, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sandrine AspeslaghAurélien Marabelle
Oct 2, 2013·Oncoimmunology·Christel DevaudMichael H Kershaw
Mar 13, 2015·Frontiers in Oncology·Stefanie N LinchWilliam L Redmond
Mar 15, 2018·Frontiers in Immunology·Mei ZhangAlex Yee-Chen Huang
May 10, 2020·Seminars in Radiation Oncology·Michael J GoughKristina H Young

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