prikaz prve stranice dokumenta Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors
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Scientific paper - Original scientific paper
Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors
Leukemia, 37 (2023); 606-617. https://doi.org/10.1038/s41375-023-01817-z
Martens, Anne W. J.; Kavazović, Inga; Krapić, Mia; Pack, Su Min; Arens, Ramon; Jongejan, Aldo; Moerland, Perry D.; Eldering, Eric; van der Windt, Gerritje J. W.; Wensveen, Felix M.; Peters, Fleur S.; Kater, Arnon P.

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Cite this document

Martens, A. W. J., Kavazović, I., Krapić, M., Pack, S. M., Arens, R., Jongejan, A. ... Kater, A. P. (2023). Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors. Leukemia, 37., 606-617. doi: 10.1038/s41375-023-01817-z

Martens, Anne W. J., et al. "Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors." Leukemia, vol. 37, 2023, pp. 606-617. https://doi.org/10.1038/s41375-023-01817-z

Martens, Anne W. J., Inga Kavazović, Mia Krapić, Su Min Pack, Ramon Arens, Aldo Jongejan, Perry D. Moerland, et al. "Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors." Leukemia 37 (2023): 606-617. https://doi.org/10.1038/s41375-023-01817-z

Martens, A. W. J., et al. (2023) 'Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors', Leukemia, 37, pp. 606-617. doi: 10.1038/s41375-023-01817-z

Martens AWJ, Kavazović I, Krapić M, Pack SM, Arens R, Jongejan A, and sur.. Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors. Leukemia [Internet]. 2023 January 19 [cited 2024 May 18];37:606-617. doi: 10.1038/s41375-023-01817-z

A. W. J. Martens, et al., "Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors", Leukemia, vol. 37, pp. 606-617, January 2023. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:153022. [Accessed: 18 May 2024]

Metadata
Title (english)Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors
AuthorAnne W. J. Martens
AuthorInga Kavazović
AuthorMia Krapić
AuthorSu Min Pack
AuthorRamon Arens
AuthorAldo Jongejan
AuthorPerry D. Moerland
AuthorEric Eldering
AuthorGerritje J. W. van der Windt
AuthorFelix M. Wensveen
AuthorFleur S. Peters
AuthorArnon P. Kater
Author's institutionUniversity of Rijeka
Faculty of Medicine
(Department of Histology and Embryology)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Abstract (english)
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+ cells to mCMV-OVA in presence/absence of TCL1 B-cell leukemia. Presence of leukemia resulted in increased SLEC formation, with disturbed inflammatory cytokine production. Chromatin and transcriptome profiling revealed strong epigenetic modifications, leading to activation of an effector and silencing of a memory profile through presence of CLL cells. Secondary challenge in vivo confirmed dysfunctional memory responses by antigen-experienced OT-I cells generated in presence of CLL. Altogether, we show that presence of CLL induces a short-lived effector phenotype and impaired memory responses by epigenetic reprogramming during primary responses.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review - international
Publication versionPublished version
Journal titleLeukemia
Numberingvol. 37, pp. 606-617
p-ISSN0887-6924
e-ISSN1476-5551
DOIhttps://doi.org/10.1038/s41375-023-01817-z
URN:NBNurn:nbn:hr:184:153022
Publication2023-01-19
Document URLhttps://www.nature.com/articles/s41375-023-01817-z
Type of resourceText
Access conditionsRestricted access
Terms of useLicence In copyright icon
Created on2023-02-27 11:05:07