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

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 pro... Full description

Journal Title: Blood October 18, 2018, Vol.132(16), pp.1675-1688
Main Author: Minnie, Simone A
Other Authors: Kuns, Rachel D , Gartlan, Kate H , Zhang, Ping , Wilkinson, Andrew N , Samson, Luke , Guillerey, Camille , Engwerda, Christian , Macdonald, Kelli P A , Smyth, Mark J , Markey, Kate A , Vuckovic, Slavica , Hill, Geoffrey R
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1528-0020 ; DOI: 10.1182/blood-2018-01-825240
Link: http://search.proquest.com/docview/2096572938/?pq-origsite=primo
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title: Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade.
format: Article
creator:
  • Minnie, Simone A
  • Kuns, Rachel D
  • Gartlan, Kate H
  • Zhang, Ping
  • Wilkinson, Andrew N
  • Samson, Luke
  • Guillerey, Camille
  • Engwerda, Christian
  • Macdonald, Kelli P A
  • Smyth, Mark J
  • Markey, Kate A
  • Vuckovic, Slavica
  • Hill, Geoffrey R
subjects:
  • Animals–Pharmacology
  • Antibodies, Monoclonal–Genetics
  • Antigens, Differentiation, T-Lymphocyte–Metabolism
  • Cd8-Positive T-Lymphocytes–Immunology
  • Cells, Cultured–Adverse Effects
  • Hematopoietic Stem Cell Transplantation–Physiology
  • Interleukin-10–Etiology
  • Mice–Pathology
  • Mice, Knockout–Prevention & Control
  • Multiple Myeloma–Antagonists & Inhibitors
  • Programmed Cell Death 1 Receptor–Immunology
  • Receptors, Immunologic–Antagonists & Inhibitors
  • Receptors, Immunologic–Immunology
  • Abridged
  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • Cd226 Antigen
  • Il10 Protein, Mouse
  • Pdcd1 Protein, Mouse
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • T Cell Ig and Itim Domain Protein, Mouse
  • Interleukin-10
ispartof: Blood, October 18, 2018, Vol.132(16), pp.1675-1688
description: 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....
language: eng
source:
identifier: E-ISSN: 1528-0020 ; DOI: 10.1182/blood-2018-01-825240
fulltext: fulltext
issn:
  • 15280020
  • 1528-0020
url: Link


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titleMyeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade.
creatorMinnie, Simone A ; Kuns, Rachel D ; Gartlan, Kate H ; Zhang, Ping ; Wilkinson, Andrew N ; Samson, Luke ; Guillerey, Camille ; Engwerda, Christian ; Macdonald, Kelli P A ; Smyth, Mark J ; Markey, Kate A ; Vuckovic, Slavica ; Hill, Geoffrey R
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ispartofBlood, October 18, 2018, Vol.132(16), pp.1675-1688
identifierE-ISSN: 1528-0020 ; DOI: 10.1182/blood-2018-01-825240
subjectAnimals–Pharmacology ; Antibodies, Monoclonal–Genetics ; Antigens, Differentiation, T-Lymphocyte–Metabolism ; Cd8-Positive T-Lymphocytes–Immunology ; Cells, Cultured–Adverse Effects ; Hematopoietic Stem Cell Transplantation–Physiology ; Interleukin-10–Etiology ; Mice–Pathology ; Mice, Knockout–Prevention & Control ; Multiple Myeloma–Antagonists & Inhibitors ; Programmed Cell Death 1 Receptor–Immunology ; Receptors, Immunologic–Antagonists & Inhibitors ; Receptors, Immunologic–Immunology ; Abridged ; Antibodies, Monoclonal ; Antigens, Differentiation, T-Lymphocyte ; Cd226 Antigen ; Il10 Protein, Mouse ; Pdcd1 Protein, Mouse ; Programmed Cell Death 1 Receptor ; Receptors, Immunologic ; T Cell Ig and Itim Domain Protein, Mouse ; Interleukin-10
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descriptionAutologous 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....
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titleMyeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade.
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titleMyeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade.
authorMinnie, Simone A ; Kuns, Rachel D ; Gartlan, Kate H ; Zhang, Ping ; Wilkinson, Andrew N ; Samson, Luke ; Guillerey, Camille ; Engwerda, Christian ; Macdonald, Kelli P A ; Smyth, Mark J ; Markey, Kate A ; Vuckovic, Slavica ; Hill, Geoffrey R
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