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Figure 7 from Single-Cell Analysis of Bone Marrow CD8+ T Cells in Myeloid Neoplasms Reveals Pathways Associated with Disease Progression and Response to Treatment with Azacitidine

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posted on 2024-12-04, 11:40 authored by Athanasios Tasis, Nikos E. Papaioannou, Maria Grigoriou, Nikolaos Paschalidis, Catherine Loukogiannaki, Anastasia Filia, Kyriaki Katsiki, Eleftheria Lamprianidou, Vasileios Papadopoulos, Christina Maria Rimpa, Antonios Chatzigeorgiou, Ioannis Kourtzelis, Petroula Gerasimou, Ioannis Kyprianou, Paul Costeas, Panagiotis Liakopoulos, Konstantinos Liapis, Petros Kolovos, Triantafyllos Chavakis, Themis Alissafi, Ioannis Kotsianidis, Ioannis Mitroulis

TF regulatory network analysis in BM-derived CD8+ T cells. A, UMAP depicting the clustering of CD8+ T cells based on regulons. B, Pie charts illustrating the representation of cells from CR and FAIL patients within each regulon. C, Comparison of cell distribution in regulons between the groups using separate UMAPs for each group. D, Heatmap showing the top differentially activated TFs of each regulon cluster. E and F, Violin plots depicting the activity score of selected TFs per sample type in regulons 5 and 7, respectively.

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ARTICLE ABSTRACT

CD8+ T cells are crucial for antitumor immunity. However, their functionality is often altered in higher-risk myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). To understand their role in disease progression, we conducted a comprehensive immunophenotypic analysis of 104 pretreatment bone marrow (BM) samples using mass and flow cytometry. Our findings revealed an increased frequency of CD57+CXCR3+ subset of CD8+ T cells in patients who did not respond to 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 single-cell RNA sequencing to assess the transcriptional profile of BM CD8+ T cells from treatment-naïve patients. The response to AZA was linked to an enrichment of IFN-mediated pathways, whereas nonresponders exhibited a heightened TGF-β signaling signature. These findings suggest that combining AZA with TGF-β signaling inhibitors targeting CD8+ T cells could be a promising therapeutic strategy for patients with higher-risk MDS and AML. Immunophenotypic analysis identified a BM CD57+CXCR3+ subset of CD8+ T cells associated with response to AZA in patients with MDS and AML. Single-cell RNA sequencing analysis revealed that IFN signaling is linked to the response to treatment, whereas TGF-β signaling is associated with treatment failure, providing insights into new therapeutic approaches.

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    Cancer Research Communications

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    Hematological CancersLeukemiasImmunologySingle Cell Technologies

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