Chronic lymphocytic leukemia presence impairs antigen-specific CD8


Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
03 2023
Historique:
received: 05 07 2022
accepted: 10 01 2023
revised: 22 12 2022
pubmed: 20 1 2023
medline: 10 3 2023
entrez: 19 1 2023
Statut: ppublish

Résumé

T-cell dysregulation in chronic lymphocytic leukemia (CLL) associates with low response rates to autologous T cell-based therapies. How CLL affects antigen-specific T-cell responses remains largely unknown. We investigated (epi)genetic and functional consequences of antigen-specific T-cell responses in presence of CLL in vitro and in an adoptive-transfer murine model. Already at steady-state, antigen-experienced patient-derived T cells were skewed towards short-lived effector cells (SLEC) at the expense of memory-precursor effector cells (MPEC). Stimulation of these T cells in vitro showed rapid induction of effector genes and suppression of key memory transcription factors only in presence of CLL cells, indicating epigenetic regulation. This was investigated in vivo by following antigen-specific responses of naïve OT-I CD8

Identifiants

pubmed: 36658390
doi: 10.1038/s41375-023-01817-z
pii: 10.1038/s41375-023-01817-z
pmc: PMC9851097
doi:

Substances chimiques

Antigens 0
Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

606-616

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Anne W J Martens (AWJ)

Department of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, Meibergdreef 9, Amsterdam, The Netherlands.

Inga Kavazović (I)

Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.

Mia Krapić (M)

Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.

Su Min Pack (SM)

Department of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, Meibergdreef 9, Amsterdam, The Netherlands.

Ramon Arens (R)

Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.

Aldo Jongejan (A)

Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Perry D Moerland (PD)

Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Eric Eldering (E)

Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, Meibergdreef 9, Amsterdam, The Netherlands.

Gerritje J W van der Windt (GJW)

Department of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, Meibergdreef 9, Amsterdam, The Netherlands.

Felix M Wensveen (FM)

Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.

Fleur S Peters (FS)

Department of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, Meibergdreef 9, Amsterdam, The Netherlands.

Arnon P Kater (AP)

Department of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. a.p.kater@amsterdamumc.nl.

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