Venetoclax treatment in patients with cancer has limited impact on circulating T and NK cells
- Author(s)
- Teh, CE; Peng, H; Luo, MX; Tan, T; Trussart, M; Howson, LJ; Chua, CC; Muttiah, C; Brown, F; Ritchie, ME; Wei, AH; Roberts, AW; Bryant, VL; Anderson, MA; Lindeman, GJ; Huang, DCS; Thijssen, R; Gray, DHD;
- Details
- Publication Year 2023-06-27,Volume 7,Issue #12,Page 2733-2745
- Journal Title
- Blood Advances
- Publication Type
- Research article
- 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.
- Publisher
- American Society of Hematology
- Keywords
- Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy; Killer Cells, Natural; *Leukemia, Myeloid, Acute/drug therapy; Bridged Bicyclo Compounds, Heterocyclic/pharmacology/therapeutic use
- Department(s)
- Clinical Haematology; Medical Oncology
- PubMed ID
- 36521105
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2022008221
- Open Access at Publisher's Site
https://doi.org/10.1182/bloodadvances.2022008221- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-10-12 07:16:42
Last Modified: 2023-10-12 07:16:59