Journal: Nature Cancer

Article Title: Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia

doi: 10.1038/s43018-025-01054-6

Figure Lengend Snippet: ( a ) SLAMF6 expression in immune cell populations based on the”Immune Cells” RNA sequencing dataset from the Human Protein Atlas. ( b ) Gene expression of SLAMF6 in major tissues based on the Human Protein Atlas RNA sequencing dataset. ( c ) SLAMF6 gene expression in major cell types in the”Single Cell Type” whole-body scRNAseq dataset from the Human Protein Atlas. ( d ) SLAMF6 protein expression in major tissues based on immunohistochemistry in the”Human Protein Atlas” dataset. ( e ) Protein expression of SLAMF6 in major tissues and cell types based on mass spectrometry in the”Human Proteome Map” dataset.

Article Snippet: Extended Data Fig. 2 SLAMF6 gene and protein expression in normal cells. ( a ) SLAMF6 expression in immune cell populations based on the”Immune Cells” RNA sequencing dataset from the Human Protein Atlas. ( b ) Gene expression of SLAMF6 in major tissues based on the Human Protein Atlas RNA sequencing dataset. ( c ) SLAMF6 gene expression in major cell types in the”Single Cell Type” whole-body scRNAseq dataset from the Human Protein Atlas. ( d ) SLAMF6 protein expression in major tissues based on immunohistochemistry in the”Human Protein Atlas” dataset. ( e ) Protein expression of SLAMF6 in major tissues and cell types based on mass spectrometry in the”Human Proteome Map” dataset.

Techniques: Expressing, RNA Sequencing, Gene Expression, Immunohistochemistry, Mass Spectrometry

Journal: Nature Cancer

Article Title: Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia

doi: 10.1038/s43018-025-01054-6

Figure Lengend Snippet: Frequencies of CD4 + T cells, CD8 + T cells and regulatory T cells within the total T cell population for each AML patient and NBM donor based on ( a ) surface protein expression by flow cytometry (n = 39 cases; Kruskal-Wallis test with Dunn’s post hoc test) and ( b ) global gene expression by single cell RNA sequencing (n = 41 cases; Kruskal-Wallis test with Dunn’s post hoc test). Similarity of T cell populations in primary AML samples to ( c ) exhausted T cells , ( d ) exhausted T cells and ( e ) progenitor exhausted T cells , based on global gene expression profiles generated by single cell RNA sequencing. ( f ) Expression of the progenitor exhausted T cell marker GZMK in T cell populations in primary AML samples. ( g ) Expression of inhibitory receptors upregulated in CD8 + T cells in AML patients . Left: All T cell populations in all AML cases (n = 41 cases). Middle: The CD4 + naïve T cell population in AML cases classified as SLAMF6 High (red; n = 11 cases), SLAMF6 Int (yellow; n = 13 cases) and SLAMF6 Neg (blue; n = 17 cases) as well as CD4 + naïve T cells from normal bone marrow (grey). Right: The CD8 + naïve T cell population in AML cases and NBM. Violin plots with bars indicating median values. Y axis scales are consistent across left, middle and right panels.

Article Snippet: Extended Data Fig. 2 SLAMF6 gene and protein expression in normal cells. ( a ) SLAMF6 expression in immune cell populations based on the”Immune Cells” RNA sequencing dataset from the Human Protein Atlas. ( b ) Gene expression of SLAMF6 in major tissues based on the Human Protein Atlas RNA sequencing dataset. ( c ) SLAMF6 gene expression in major cell types in the”Single Cell Type” whole-body scRNAseq dataset from the Human Protein Atlas. ( d ) SLAMF6 protein expression in major tissues based on immunohistochemistry in the”Human Protein Atlas” dataset. ( e ) Protein expression of SLAMF6 in major tissues and cell types based on mass spectrometry in the”Human Proteome Map” dataset.

Techniques: Expressing, Flow Cytometry, Gene Expression, RNA Sequencing, Generated, Marker

Journal: Nature Cancer

Article Title: Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia

doi: 10.1038/s43018-025-01054-6

Figure Lengend Snippet: ( a ) T cell activation in response to in vitro treatment with TNC-1 in co-cultures with primary T cells and HNT-34 cells (left; p = 0.041), KG-1 cells (middle; p = 0.314) and THP-1 cells (right; p = 0.364), as determined by surface marker expression of CD25 and CD69. Mean ± SEM of four (KG-1) or six (HNT-34, THP-1) T cell donors, normalized to isotype control (two-sided Mann-Whitney U test). ( b ) AML cell killing in response to treatment with TNC-1 in suspension cultures without T cells, containing only HNT-34 cells (left; p = 0.999), KG-1 cells (middle; p = 0.700) and THP-1 cells (right; p = 0.999). Mean ± SEM of four experiments, normalized to isotype control (two-sided Mann-Whitney U test). ( c ) T cell-mediated killing of AML cells over time in co-cultures with T cells expressing the NY-ESO T cell receptor and HNT-34 AML cells expressing the corresponding peptide-MHC complex. Mean ± SEM of four technical replicates for each time point and treatment condition for one T cell donor (two-sided Mann-Whitney U test; p = 0.029 for all time points). ( d ) T cell activation after 72 h in the NY-ESO co-culture model, as determined by surface expression of CD25. Mean ± SEM of three T cell donors (two-sided Mann-Whitney U test; p = 0.999). ( e ) UMAP projection and cell type classifications for co-cultures with T cells and HNT-34 AML cells after treatment with TNC-1 (left; n = 16254 cells) or an isotype control antibody (right; n = 15723 cells), based on single-cell RNA sequencing. Joint projection for co-cultures with two independent T cell donors. MAIT: mucosal-associated invariant T cell, Treg: regulatory T cell, gdT: gamma delta T cell, NK: natural killer cell. ( f ) Volcano plot of differentially expressed genes between HNT-34 cells treated with TNC-1 or an isotype control antibody in T cell co-cultures (n = 23886 genes). Y axis represents significance denoted as the negative logarithm of the p value (two-sided t test, without multiple testing correction). Grey: P value > 10 −5 . Blue: P value < 10 −5 . ( g ) The 15 most significantly downregulated (left) and upregulated (right) gene sets in HNT-34 cells treated with TNC-1 compared to treatment with an isotype control antibody, based on gene set enrichment analysis (GSEA) using the Reactome database (fgsea test with multiple testing correction and threshold p < 0.05). ( h ) Distribution of T cell populations in two independent donors after treatment with TNC-1 or an isotype control antibody, based on single-cell RNA sequencing analysis.

Article Snippet: Extended Data Fig. 2 SLAMF6 gene and protein expression in normal cells. ( a ) SLAMF6 expression in immune cell populations based on the”Immune Cells” RNA sequencing dataset from the Human Protein Atlas. ( b ) Gene expression of SLAMF6 in major tissues based on the Human Protein Atlas RNA sequencing dataset. ( c ) SLAMF6 gene expression in major cell types in the”Single Cell Type” whole-body scRNAseq dataset from the Human Protein Atlas. ( d ) SLAMF6 protein expression in major tissues based on immunohistochemistry in the”Human Protein Atlas” dataset. ( e ) Protein expression of SLAMF6 in major tissues and cell types based on mass spectrometry in the”Human Proteome Map” dataset.

Techniques: Activation Assay, In Vitro, Marker, Expressing, Control, MANN-WHITNEY, Suspension, Co-Culture Assay, RNA Sequencing

Journal: Nature Cancer

Article Title: Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia

doi: 10.1038/s43018-025-01054-6

Figure Lengend Snippet: Similarity of T cell populations to ( a ) progenitor exhausted T cells and ( b ) exhausted T cells after treatment of T cell and AML cell co-cultures with TNC-1 or an isotype control antibody for 72 h, based on gene expression profiles determined by single-cell RNA sequencing. Violin plots with bars indicating median values. Red: Distributions of T cells treated with TNC-1. Blue: Distributions of T cells treated with an isotype control antibody. ( c ) Frequencies of CD4 + and CD8 + T cells after treatment with TNC-1 in co-culture experiments with primary T cells and HNT-34 AML cells. ( d ) Composition of the CD4 + T cell population in co-cultures, based on surface expression of CD45RA and CCR7. ( e ) Composition of the CD8 + T cell population in co-cultures, based on surface expression of CD45RA and CCR7. ( f ) Expression of T cell inhibitory receptors and exhaustion markers after treatment with TNC-1. All data is based on surface marker profiling by flow cytometry. Mean of four technical replicates for each donor and treatment condition.

Article Snippet: Extended Data Fig. 2 SLAMF6 gene and protein expression in normal cells. ( a ) SLAMF6 expression in immune cell populations based on the”Immune Cells” RNA sequencing dataset from the Human Protein Atlas. ( b ) Gene expression of SLAMF6 in major tissues based on the Human Protein Atlas RNA sequencing dataset. ( c ) SLAMF6 gene expression in major cell types in the”Single Cell Type” whole-body scRNAseq dataset from the Human Protein Atlas. ( d ) SLAMF6 protein expression in major tissues based on immunohistochemistry in the”Human Protein Atlas” dataset. ( e ) Protein expression of SLAMF6 in major tissues and cell types based on mass spectrometry in the”Human Proteome Map” dataset.

Techniques: Control, Gene Expression, RNA Sequencing, Co-Culture Assay, Expressing, Marker, Flow Cytometry

Journal: Nature Cancer

Article Title: Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia

doi: 10.1038/s43018-025-01054-6

Figure Lengend Snippet: Increased expression of genes associated with T cell activation in T cell populations from ( a ) Donor U and ( b ) Donor W after treatment with TNC-1 compared to an isotype control antibody, based on gene set enrichment analysis of single-cell RNA sequencing data. ( c ) The 15 most significantly upregulated (left) and downregulated (right) gene sets in cells classified as CD8 + effector T cells after treatment of co-cultures containing primary T cells from Donor U and HNT-34 cells with TNC-1 compared to an isotype control antibody, based on gene set enrichment analysis (GSEA) of single-cell RNA sequencing data using the Reactome database. ( d ) Gene sets upregulated (left) and downregulated (right) in CD8 + effector T cells from Donor W after treatment of co-cultures with TNC-1. ( e ) Gene sets upregulated (left) and downregulated (right) in CD8 + memory T cells from Donor U after treatment of co-cultures with TNC-1. ( f ) Gene sets upregulated (left) and downregulated (right) in CD8 + memory T cells from Donor W after treatment of co-cultures with TNC-1. All p values are based on the fgsea test with correction for multiple testing. Gene sets are included with a significance threshold of p < 0.05.

Article Snippet: Extended Data Fig. 2 SLAMF6 gene and protein expression in normal cells. ( a ) SLAMF6 expression in immune cell populations based on the”Immune Cells” RNA sequencing dataset from the Human Protein Atlas. ( b ) Gene expression of SLAMF6 in major tissues based on the Human Protein Atlas RNA sequencing dataset. ( c ) SLAMF6 gene expression in major cell types in the”Single Cell Type” whole-body scRNAseq dataset from the Human Protein Atlas. ( d ) SLAMF6 protein expression in major tissues based on immunohistochemistry in the”Human Protein Atlas” dataset. ( e ) Protein expression of SLAMF6 in major tissues and cell types based on mass spectrometry in the”Human Proteome Map” dataset.

Techniques: Expressing, Activation Assay, Control, RNA Sequencing