Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade.

Blood
Simone A MinnieGeoffrey R Hill

Abstract

Autologous stem cell transplantation (SCT) remains a standard of care for multiple myeloma (MM) patients and prolongs progression-free survival. A small cohort of patients achieve long-term control of disease, but the majority of patients ultimately relapse, and the mechanisms permitting disease progression remain unclear. In this study, we used a preclinical model of autologous SCT for myeloma where the disease either progressed (MM relapsed) or was controlled. In the bone marrow (BM), inhibitory receptor expression on CD8+ T cells correlated strongly with myeloma progression after transplant. In conjunction, the costimulatory/adhesion receptor CD226 (DNAM-1) was markedly downregulated. Interestingly, DNAM-1- CD8+ T cells in MM-relapsed mice had an exhausted phenotype, characterized by upregulation of multiple inhibitory receptors, including T-cell immunoglobulin and ITIM domains (TIGIT) and programmed cell death protein 1 (PD-1) with decreased T-bet and increased eomesodermin expression. Immune checkpoint blockade using monoclonal antibodies against PD-1 or TIGIT significantly prolonged myeloma control after SCT. Furthermore, CD8+ T cells from MM-relapsed mice exhibited high interleukin-10 (IL-10) secretion that was associate...Continue Reading

References

Aug 1, 2002·Leukemia & Lymphoma·Takemi OtsukiAyako Ueki
May 9, 2003·The New England Journal of Medicine·J Anthony ChildUNKNOWN Medical Research Council Adult Leukaemia Working Party
Jul 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kelli P A MacDonaldGeoffrey R Hill
Sep 22, 2005·Immunology and Cell Biology·Alberto Pinzon-CharryJ Alejandro López
Oct 15, 2005·The Journal of Clinical Investigation·Edward S MorrisGeoffrey R Hill
Oct 1, 2009·Blood·Kate A MarkeyGeoffrey R Hill
Apr 13, 2011·Blood·Joaquin Martinez-LopezUNKNOWN Programa para el Estudio de la Terapé utica en Hemopatía Maligna
Apr 13, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Philippe MoreauMichel Attal
May 4, 2011·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·William H D HallettBryon D Johnson
Dec 17, 2011·Cancer Cell·John B MummMartin Oft
Apr 26, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tyce J KearlBryon D Johnson
Jul 23, 2013·Frontiers in Immunology·Kristian M Hargadon
Jan 24, 2015·Journal for Immunotherapy of Cancer·Weiqing JingBryon D Johnson
Mar 7, 2015·Pathology Oncology Research : POR·Michael G AlexandrakisGeorge Tsirakis
Mar 24, 2015·Trends in Immunology·Kristen E Pauken, E John Wherry
Apr 22, 2015·The Journal of Clinical Investigation·Camille GuillereyLudovic Martinet
May 2, 2015·European Journal of Immunology·Romain Vuillefroy de SillyPaul R Walker
Jul 25, 2015·Nature Reviews. Immunology·E John Wherry, Makoto Kurachi
Oct 16, 2015·Cancer Immunology Research·David J ChungJames W Young
Jan 15, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yaxian KongHong Zheng
Feb 18, 2016·British Journal of Cancer·Hua WangYue Lu
Jun 9, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alexander M LesokhinJohn Timmerman
Nov 5, 2016·Journal of Hematology & Oncology·Claudia Zelle-RieserKarin Jöhrer
Nov 15, 2016·Nature Medicine·Marta ChesiP Leif Bergsagel
May 11, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jianjun XiJianwen Bai
May 18, 2017·Nature·Mary PhilipAndrea Schietinger
Jul 21, 2017·Nature Reviews. Disease Primers·Shaji K KumarKenneth C Anderson
Jul 25, 2017·Science Immunology·Ping ZhangGeoffrey R Hill
Feb 15, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Catherine A HawleyStephen J Jenkins

❮ Previous
Next ❯

Citations

Nov 21, 2018·The Journal of Clinical Investigation·Shuai Dong, Irene M Ghobrial
Oct 10, 2018·The Journal of Clinical Investigation·Slavica VuckovicGeoffrey R Hill
Jan 11, 2019·Cancers·Alexander David Barrow, Marco Colonna
May 10, 2019·Expert Review of Hematology·Abdullah M KhanDon M Benson
Oct 20, 2018·Blood·Fotis Asimakopoulos
Dec 13, 2019·Clinical and Experimental Immunology·H Harjunpää, C Guillerey
May 10, 2020·Journal of Cellular Physiology·Abbas HajifathaliMajid Gholizadeh
Apr 22, 2020·Nature Reviews. Clinical Oncology·Bruce R BlazarWilliam J Murphy
Mar 10, 2020·The Journal of Clinical Investigation·Simone A Minnie, Geoffrey R Hill
Aug 10, 2020·Bone Marrow Transplantation·Binod DhakalMehdi Hamadani
May 17, 2019·Journal of Oncology·Rachel E CookeDavid Ritchie
Jan 9, 2019·Frontiers in Immunology·Jing LiChen Dong
Dec 18, 2019·Cancers·Hideto TamuraKoiti Inokuchi
Aug 14, 2020·Journal of Hematology & Oncology·Basit SalikKyohei Nakamura
Mar 3, 2020·Frontiers in Immunology·Muhammad KhanHua Wang
Jul 10, 2020·Blood·Kyohei NakamuraLudovic Martinet
Aug 3, 2019·Cancer Immunology Research·Alexander M LesokhinAshraf Z Badros
Nov 2, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adam D CohenMadhav V Dhodapkar
Jun 10, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ester LozanoCarlos Fernández de Larrea
Jan 14, 2021·Cancers·Almudena García-OrtizJoaquín Martínez-López
Dec 12, 2020·Frontiers in Immunology·Helmi AlfarraTony Reiman
Feb 11, 2021·Cancers·Raquel LopesCristina João
Feb 19, 2021·Leukemia·Mohamed H S AwwadMichael Hundemer
Mar 9, 2021·Frontiers in Immunology·Anne Marit SponaasTherese Standal
Mar 7, 2021·Pharmaceuticals·Jinah YeoHyung-Seung Jin
Mar 16, 2021·Frontiers in Immunology·Samuel S McCachrenMadhav V Dhodapkar
Mar 27, 2021·Stem Cell Research & Therapy·Margaret G LambDean A Lee
Mar 30, 2021·Frontiers in Immunology·Simone A Minnie, Geoffrey R Hill
Apr 4, 2021·Cancers·Raquel LopesCristina João
Feb 20, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hyunsoo ChoJin Seok Kim
Jun 12, 2021·Journal for Immunotherapy of Cancer·Kevin Jan LegschaHakim Echchannaoui

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Related Papers

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
William H D HallettBryon D Johnson
Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research
B HeegP Sonneveld
© 2022 Meta ULC. All rights reserved