Natural Killer T-Cell Agonist α-Galactosylceramide and PD-1 Blockade Synergize to Reduce Tumor Development in a Preclinical Model of Colon Cancer.

Frontiers in Immunology
Ying WangSusanna L Cardell

Abstract

Murine and human invariant natural killer T (iNKT) lymphocytes are activated by α-galactosylceramide (α-GalCer) presented on CD1d. α-GalCer was first described as a lipid that had strong anti-metastatic effects in a mouse melanoma model, and it has subsequently been shown to induce efficient iNKT cell dependent tumor immunity in several tumor models. We have shown that α-GalCer treatment leads to a weak reduction of polyp burden in the autochthonous ApcMin/+ mouse model for human colon cancer, however this treatment resulted in upregulation of the inhibitory receptor PD-1 on iNKT cells. While anti-PD-1 treatment can prevent immune-suppression in other cancer types, human colon cancer is generally resistant to this treatment. Here we have used the ApcMin/+ model to investigate whether a combined treatment with α-GalCer and PD-1 blockade results in improved effects on polyp development. We find that PD-1 expression was high on T cells in polyps and lamina propria (LP) of ApcMin/+ mice compared to polyp free Apc+/+ littermates. Anti-PD-1 treatment alone promoted Tbet expression in iNKT cells and CD4 T cells, but did not significantly reduce polyp numbers. However, the combined treatment with anti-PD-1 and α-GalCer had synergistic ...Continue Reading

References

Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Reade B RobertsDavid W Threadgill
Mar 25, 2004·Nature Reviews. Immunology·Dale I GodfreyLuc Van Kaer
Jul 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomohide YamazakiKo Okumura
Sep 3, 2005·The Journal of Clinical Investigation·Vrajesh V ParekhLuc Van Kaer
Oct 21, 2006·Cancer Science·Yasuhiro Yamada, Hideki Mori
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Woo-Sung ChangChang-Yuil Kang
Dec 6, 2008·Advances in Cancer Research·Masaki Terabe, Jay A Berzofsky
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vrajesh V ParekhLuc Van Kaer
Nov 26, 2010·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Leonid S Metelitsa
Jan 18, 2011·Cancer Immunology, Immunotherapy : CII·Kevin DurganYvette E Latchman
Oct 4, 2011·The Journal of Clinical Investigation·Elizabeth A WohlfertYasmine Belkaid
Dec 18, 2012·Science Translational Medicine·Nichole R BlatnerKhashayarsha Khazaie
Jan 5, 2014·Cancer Immunology, Immunotherapy : CII·Masaki Terabe, Jay A Berzofsky
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Sep 29, 2015·The Journal of Pathology·Rene Jackstadt, Owen J Sansom
Mar 26, 2016·Biomedical Journal·Celine TardAgnes Lehuen
Apr 9, 2016·Oncoimmunology·Mihaela AngelovaZ Trajanoski
May 20, 2016·Clinical & Translational Immunology·Leandro J CarreñoSteven A Porcelli
Jul 3, 2016·Immunogenetics·Catherine M Crosby, Mitchell Kronenberg
Oct 12, 2017·Frontiers in Immunology·Shiny Nair, Madhav V Dhodapkar
Jan 13, 2018·Frontiers in Immunology·Melissa BedardVincenzo Cerundolo
Mar 22, 2018·Frontiers in Immunology·Benjamin J WolfMark A Exley
Mar 22, 2018·Immunity·Dale I GodfreyJamie Rossjohn
Jul 4, 2018·Nature Reviews. Immunology·Catherine M Crosby, Mitchell Kronenberg
Aug 18, 2018·Cancer Discovery·Spencer C WeiJames P Allison
Oct 17, 2019·Przegla̜d gastroenterologiczny·Prashanth RawlaAdam Barsouk

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

FlowJo
Prism GraphPad
GraphPad

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