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Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment

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  1. Clonotypic heterogeneity in cutaneous T-cell lymphoma (mycosis fungoides) revealed by comprehensive whole-exome sequencing

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  2. Proteomic profiling identifies outcome-predictive markers in patients with peripheral T-cell lymphoma, not otherwise specified

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  3. Single-cell heterogeneity in Sézary syndrome

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  4. Human adult HSCs can be discriminated from lineage-committed HPCs by the expression of endomucin

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  5. Stringent or nonstringent complete remission and prognosis in acute myeloid leukemia: a Danish population-based study

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  1. The Number of Signaling Pathways Altered by Driver Mutations in Chronic Lymphocytic Leukemia Impacts Disease Outcome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Machine learning can identify newly diagnosed patients with CLL at high risk of infection

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Ibrutinib and Venetoclax for First-Line Treatment of CLL

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Blodsygdomme

    Publikation: Bidrag til bog/antologi/rapportBidrag til bog/antologiFormidling

  5. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Iris de Weerdt
  • Tom Hofland
  • Renate de Boer
  • Johan A Dobber
  • Julie Dubois
  • Denise van Nieuwenhuize
  • Mehrdad Mobasher
  • Fransien de Boer
  • Mels Hoogendoorn
  • Gerjo A Velders
  • Marjolein van der Klift
  • Ester B M Remmerswaal
  • Frederike J Bemelman
  • Carsten U Niemann
  • Sabina Kersting
  • Mark-David Levin
  • Eric Eldering
  • Sanne H Tonino
  • Arnon P Kater
Vis graf over relationer

Morbidity and mortality due to immunosuppression remain among the foremost clinical challenges in chronic lymphocytic leukemia (CLL). Although immunosuppression is considered to originate within the lymph node (LN) microenvironment, alterations in T and natural killer (NK) cells have almost exclusively been studied in peripheral blood (PB). Whereas chemoimmunotherapy further deteriorates immune function, novel targeted agents like the B-cell lymphoma 2 inhibitor venetoclax potentially spare nonmalignant lymphocytes; however, the effects of venetoclax on nonleukemic cells have not been explored. We address these unresolved issues using a comprehensive analysis of nonmalignant lymphocytes in paired LN and PB samples from untreated CLL patients, and by analyzing the effects of venetoclax-based treatment regimens on the immune system in PB samples from previously untreated and relapsed/refractory patients. CLL-derived LNs contained twice the amount of suppressive regulatory T cells (Tregs) and CLL supportive follicular T helper (Tfh) cells compared with PB. This was accompanied by a low frequency of cytotoxic lymphocytes. The expression of PD-1 by CD8+ T cells was significantly higher in LN compared with PB. Venetoclax-based treatment led to deep responses in the majority of patients, but also to decreased absolute numbers of B, T, and NK cells. Tfh cell, Treg, and PD-1+ CD8+ T cell numbers were reduced more than fivefold after venetoclax-based therapy, and overproduction of inflammatory cytokines was reduced. Furthermore, we observed restoration of NK cell function. These data support the notion that the immunosuppressive state in CLL is more prominent within the LN. Venetoclax-based regimens reduced the immunosuppressive footprint of CLL, suggesting immune recovery after the elimination of leukemic cells.

OriginalsprogEngelsk
TidsskriftBlood advances
Vol/bind3
Udgave nummer17
Sider (fra-til)2642-2652
Antal sider11
ISSN2473-9529
DOI
StatusUdgivet - 10 sep. 2019

Bibliografisk note

© 2019 by The American Society of Hematology.

ID: 58441968