Artikel ; Online: Venetoclax treatment in patients with cancer has limited impact on circulating T and NK cells.
2022 Band 7, Heft 12, Seite(n) 2733–2745
Abstract: Venetoclax is an effective treatment for certain blood cancers, such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, most patients relapse while on venetoclax and further treatment options are limited. Combining ... ...
Abstract | Venetoclax is an effective treatment for certain blood cancers, such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, most patients relapse while on venetoclax and further treatment options are limited. Combining venetoclax with immunotherapies is an attractive approach; however, a detailed understanding of how venetoclax treatment impacts normal immune cells in patients is lacking. In this study, we performed deep profiling of peripheral blood (PB) cells from patients with CLL and AML before and after short-term treatment with venetoclax using mass cytometry (cytometry by time of flight) and found no impact on the concentrations of key T-cell subsets or their expression of checkpoint molecules. We also analyzed PB from patients with breast cancer receiving venetoclax long-term using a single-cell multiomics approach (cellular indexing of transcriptomes and epitopes by sequencing) and functional assays. We found significant depletion of B-cell populations with low expression of MCL-1 relative to other immune cells, attended by extensive transcriptomic changes. By contrast, there was less impact on circulating T cells and natural killer (NK) cells, with no changes in their subset composition, transcriptome, or function following venetoclax treatment. Our data indicate that venetoclax has minimal impact on circulating T or NK cells, supporting the rationale of combining this BH3 mimetic drug with cancer immunotherapies for more durable antitumor responses. |
---|---|
Mesh-Begriff(e) | Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/drug therapy ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use |
Chemische Substanzen | venetoclax (N54AIC43PW) ; Bridged Bicyclo Compounds, Heterocyclic |
Sprache | Englisch |
Erscheinungsdatum | 2022-12-14 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article |
ZDB-ID | 2915908-8 |
ISSN | 2473-9537 ; 2473-9529 |
ISSN (online) | 2473-9537 |
ISSN | 2473-9529 |
DOI | 10.1182/bloodadvances.2022008221 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
Zs.A 7153: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.