Venetoclax treatment in cancer patients has limited impact on circulating T and NK cells

Teh, CE; Peng, H; Luo, M; Tan, T; Trussart, M; Howson, LJ; Chua, CC; Muttiah, C; Brown, FC; Ritchie, ME; Wei, AH; Roberts, AW; Bryant, VL; Anderson, MA; Lindeman, GJ; Huang, DCS; Thijssen, R; Gray, DHD

Author(s): Teh, CE; Peng, H; Luo, M; Tan, T; Trussart, M; Howson, LJ; Chua, CC; Muttiah, C; Brown, FC; Ritchie, ME; Wei, AH; Roberts, AW; Bryant, VL; Anderson, MA; Lindeman, GJ; Huang, DCS; Thijssen, R; Gray, DHD;
Details: Publication Year 2023-12-15,Volume 7,Issue #12,Page 2733-2745
Journal Title: Blood Advances
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 become 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 cells from CLL and AML patients before and after short-term treatment with venetoclax using mass cytometry (CyTOF) and found no impact on the concentrations of key T cell subsets nor their expression of checkpoint molecules. We also analyzed peripheral blood from breast cancer patients receiving venetoclax long-term using a single-cell multi-omics approach (CITE-seq) 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 anti-tumour responses.
Publisher: ASH
Keywords: Humans; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy; Killer Cells, Natural; Leukemia, Myeloid, Acute/drug therapy; Bridged Bicyclo Compounds, Heterocyclic/pharmacology/therapeutic use
Research Division(s): Immunology; Bioinformatics; Blood Cells And Blood Cancer; Cancer Biology And Stem Cells; Epigenetics And Development; Inflammation; Blood Cells and Blood Cancer; Inflammation; Bioinformatics; Cancer Biology and Stem Cells; Epigenetics and Development
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: 2022-12-22 08:38:59

Last Modified: 2023-06-21 08:55:55