Tasis, Athanasios, Papaioannou, Nikos E, Grigoriou, Maria et al. (19 more authors) (2024) Single-cell analysis of bone marrow CD8+ T cells in Myeloid Neoplasms reveals pathways associated with disease progression and response to treatment with Azacitidine. Cancer research communications. ISSN 2767-9764
Abstract
CD8+ T cells are crucial for antitumor immunity. In higher-risk myelodysplastic neoplasms (HR-MDS) and acute myeloid leukemia (AML), CD8+ T cells exhibit altered functionality. To address their role in the course of the disease, we performed in-depth immunophenotypic analysis of 104 pre-treatment bone marrow (BM) samples using mass and flow cytometry and observed an increased frequency of the CD57+CXCR3+ subset of CD8+ T cells in patients who failed azacitidine (AZA) therapy. Furthermore, an increased baseline frequency (>29%) of the CD57+CXCR3+CD8+ T cell subset was correlated with poor overall survival. We performed scRNA-seq to assess the transcriptional profile of BM CD8+ T cells from treatment-naive patients. The response to AZA was positively associated with the enrichment of IFN-mediated pathways, whereas an enhanced TGF-β signaling signature was observed in non-responders. Our results suggest that targeting CD8+ T cells with inhibitors of TGF-β signaling in combination with AZA is a potential therapeutic strategy for HR-MDS and AML.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 15 Nov 2024 10:20 |
Last Modified: | 27 Jan 2025 00:09 |
Published Version: | https://doi.org/10.1158/2767-9764.CRC-24-0310 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1158/2767-9764.CRC-24-0310 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:219692 |
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Filename: crc-24-0310.pdf
Description: Single-cell analysis of bone marrow CD8+ T cells in Myeloid Neoplasms reveals pathways associated with disease progression and response to treatment with Azacitidine
Licence: CC-BY 2.5