CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies.

Blood
Mohamad F Al SayedAdrian F Ochsenbein

Abstract

The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells. Similar to other TNFR ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on malignant cells increased the number of tumor-infiltrating interferon γ-producing natural killer (NK) cells. In contrast, the antitumoral T-cell response remained largely unchanged. CD70 reverse signaling in NK cells was mediated via the AKT signaling pathway and increased NK cell survival and effector function. The improved immune control by activated NK cells prolonged survival of CD27-trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced survival and effector function of human NK cells in a B-cell acu...Continue Reading

References

Jul 1, 1994·International Immunology·P MombaertsA K Bhan
Jun 10, 1998·International Immunology·H OshimaK Okumura
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·A F OchsenbeinR M Zinkernagel
Jul 27, 1999·Cytokine·B Erlichman, O M Howard
Aug 25, 1999·British Journal of Haematology·S M LensM H van Oers
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·K TakedaK Okumura
Apr 27, 2000·Immunology Today·K AgematsuA Komiyama
May 9, 2000·The American Journal of Surgical Pathology·T HishimaM Koike
Sep 7, 2000·The Journal of Experimental Medicine·M J SmythJ A Trapani
Feb 13, 2001·The International Journal of Biochemistry & Cell Biology·H Wajant, P Scheurich
Mar 29, 2002·International Journal of Cancer. Journal International Du Cancer·Janka Held-Feindt, Rolf Mentlein
Dec 7, 2002·Nature Immunology·Kiki TesselaarRené A W van Lier
Dec 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kiki TesselaarRené A W van Lier
Apr 11, 2003·Leukemia & Lymphoma·Henry Y DongDavid M Dorfman
Jun 6, 2003·Current Opinion in Immunology·Lewis L Lanier
Mar 23, 2004·Annual Review of Immunology·Wayne M YokoyamaAnthony R French
Jul 1, 2004·Journal of Leukocyte Biology·Pilar GarcíaMiguel López-Botet
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ramon ArensMarinus H J van Oers
Nov 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert L CampDavid L Rimm
May 10, 2005·The Journal of Urology·Kerstin JunkerJoerg Schubert
May 12, 2005·Current Opinion in Immunology·Jannie BorstYanling Xiao
Jun 9, 2006·The New England Journal of Medicine·Sandeep S DaveUNKNOWN Lymphoma/Leukemia Molecular Profiling Project
Aug 23, 2006·The Journal of Experimental Medicine·Matthias MatterAdrian F Ochsenbein
Mar 6, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Andrew E GrulichWendy Cozen
Jun 6, 2007·International Immunology·Michiel F van OosterwijkRené A W van Lier
Aug 3, 2007·Cancer Research·Matthias MatterAdrian F Ochsenbein
Apr 24, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Aude BonehillKris Thielemans
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Paul BolithoMark J Smyth
Oct 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cathrien R L BeishuizenKlaas P J M van Gisbergen
Jan 11, 2012·The Journal of Clinical Investigation·Christian SchürchAdrian F Ochsenbein

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Citations

Jun 13, 2019·Journal of Hematology & Oncology·Hao WangXingxing Zang
Apr 23, 2020·American Journal of Respiratory Cell and Molecular Biology·Thi K Tran-NguyenSteven R Duncan
May 21, 2020·Cells·Malak Hassn MesratiAmir Syahir
Jul 22, 2017·Blood·Todd A Fehniger
Jan 4, 2018·Oncoimmunology·Tamara HilmenyukAdrian F Ochsenbein
Dec 12, 2018·International Journal of Cardiology·Wei LiKai Huang

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