Robert L. Bartoszek
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View article: TET2 regulates early and late transitions in exhausted CD8 <sup>+</sup> T cell differentiation and limits CAR T cell function
TET2 regulates early and late transitions in exhausted CD8 <sup>+</sup> T cell differentiation and limits CAR T cell function Open
CD8 + T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting TET2 in CAR T cells provides therapeutic benefit; however, TET2’s role in exhausted T cell (T EX…
View article: Figure S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Impact of EGR2 knockout on CD8+/CD4+ ratio and Th2 cytokine production in the setting of chronic tumor antigen stimulation. A, Comparison of CD8+/CD4+ ratio in control and EGR2 knockout (KO) CAR T-cells after chronic CAR stimulation. B, Th…
View article: Figure S8 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S8 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Comparison of Type I IFN gene expression in different CAR-T engineering approaches. (A-F) show volcano plots and a heatmap of gene expression in engineered CAR T-cells, with type I IFN genes highlighted in blue. These data represent differ…
View article: Figure S5 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S5 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Gene expression and pathway enrichment analysis of CD8+ T cell clusters. A, Heatmap showing differentially expressed genes between memory-like KLF2+ and exhausted-like MKI67+ CD8+ T-cells. Gene signature scores related to cell cycle and cl…
View article: Figure S7 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S7 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Gene expression and pathway enrichment analysis of CD4+ T cell clusters. (A) Heatmap showing differentially expressed genes between AAVS1 and EGR2 knockout (KO) CD4+ T-cells. (B-D) Top differentially regulated pathways in CD4+ EGR2 KO comp…
View article: Table S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Table S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Genes deferentially expressed in EGR2 compared to AAVS1 knockout CD8+ CAR T-cells. The corresponding log2 fold change values and statistical significance are provided for the listed genes.
View article: Figure S11 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S11 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Analysis of survival outcomes and EGR2 gene expression in CD19 CAR T-cell products. The figure presents the P values and hazard ratio of different EGR2 molecular marker stratification points in relation to A, overall survival and B, event-…
View article: Figure S7 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S7 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Gene expression and pathway enrichment analysis of CD4+ T cell clusters. (A) Heatmap showing differentially expressed genes between AAVS1 and EGR2 knockout (KO) CD4+ T-cells. (B-D) Top differentially regulated pathways in CD4+ EGR2 KO comp…
View article: Figure S9 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S9 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Epigenetic remodeling of CAR T-cells by EGR2 knockout and effect of type I IFN signaling on the development of memory and exhaustion. A, Volcano plots showing differentially accessible chromatin regions within genes between KLF2+ and MKI67…
View article: Figure S6 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S6 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Pathways regulated by EGR2 in CD8+ CAR T-cells. (A-C) Top pathways differentially expressed in EGR2 knockout CD8+ CAR-T cells compared to AAVS1 knockout CAR T-cells. Libraries used in this enrichment analysis: A, Reactome 2016. B, NCI-Natu…
View article: Table S3 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Table S3 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Chromatin accessibility profiles for EGR2 knockout (KO) and AAVS1 knockout (AAVS1) CD8+ CAR T-cells. The table provides information on the locus mapping, p-value, average log2 fold change, percentage of cells, adjusted p-value, transcript …
View article: Figure S3 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S3 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Impact of EGR2 knockout on different T-cell subsets and CD28-based CAR T-cells. A, Naive, central memory, effector memory, and effector T-cells were magnetically isolated. PSMA CAR-T cells with AAVS1 and EGR2 knockout (KO) were then genera…
View article: Table S3 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Table S3 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Chromatin accessibility profiles for EGR2 knockout (KO) and AAVS1 knockout (AAVS1) CD8+ CAR T-cells. The table provides information on the locus mapping, p-value, average log2 fold change, percentage of cells, adjusted p-value, transcript …
View article: Figure S11 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S11 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Analysis of survival outcomes and EGR2 gene expression in CD19 CAR T-cell products. The figure presents the P values and hazard ratio of different EGR2 molecular marker stratification points in relation to A, overall survival and B, event-…
View article: Figure S8 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S8 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Comparison of Type I IFN gene expression in different CAR-T engineering approaches. (A-F) show volcano plots and a heatmap of gene expression in engineered CAR T-cells, with type I IFN genes highlighted in blue. These data represent differ…
View article: Table S1 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Table S1 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Genes comprising the TCF7 regulon, the type I IFN signature, and the EGR2 Co-expression signatures. Gene names and symbols are listed.
View article: Figure S9 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S9 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Epigenetic remodeling of CAR T-cells by EGR2 knockout and effect of type I IFN signaling on the development of memory and exhaustion. A, Volcano plots showing differentially accessible chromatin regions within genes between KLF2+ and MKI67…
View article: Figure S1 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S1 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Analysis of EGR2 and type I IFN pathway regulation in CAR T-cells. (A-C) ATAC-seq tracks of genes associated with dysfunction, type I IFN signaling, and memory differentiation are shown, with differentially accessible regions indicated. D,…
View article: Figure S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Impact of EGR2 knockout on CD8+/CD4+ ratio and Th2 cytokine production in the setting of chronic tumor antigen stimulation. A, Comparison of CD8+/CD4+ ratio in control and EGR2 knockout (KO) CAR T-cells after chronic CAR stimulation. B, Th…
View article: Figure S10 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S10 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
EGR2 knockout enhances the long-term potency and memory function of CAR T-cells in vivo. A, Schematic of the tumor rechallenge experiments. B, Tumor growth after the first (left) and second (right) NALM6 challenges (Mann-Whitney test, n = …
View article: Figure S5 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S5 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Gene expression and pathway enrichment analysis of CD8+ T cell clusters. A, Heatmap showing differentially expressed genes between memory-like KLF2+ and exhausted-like MKI67+ CD8+ T-cells. Gene signature scores related to cell cycle and cl…
View article: Figure S4 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S4 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Marker gene expression in CAR T-cell clusters. A, Uniform manifold approximation and projection (UMAP) plot of AAVS1 and EGR2 knockout (KO) CAR T-cell samples is shown. B, UMAP plots showing expression levels of CD4 and CD8. C, Violin plot…
View article: Figure S4 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S4 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Marker gene expression in CAR T-cell clusters. A, Uniform manifold approximation and projection (UMAP) plot of AAVS1 and EGR2 knockout (KO) CAR T-cell samples is shown. B, UMAP plots showing expression levels of CD4 and CD8. C, Violin plot…
View article: Figure S10 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S10 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
EGR2 knockout enhances the long-term potency and memory function of CAR T-cells in vivo. A, Schematic of the tumor rechallenge experiments. B, Tumor growth after the first (left) and second (right) NALM6 challenges (Mann-Whitney test, n = …
View article: Figure S1 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S1 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Analysis of EGR2 and type I IFN pathway regulation in CAR T-cells. (A-C) ATAC-seq tracks of genes associated with dysfunction, type I IFN signaling, and memory differentiation are shown, with differentially accessible regions indicated. D,…
View article: Figure S6 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S6 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Pathways regulated by EGR2 in CD8+ CAR T-cells. (A-C) Top pathways differentially expressed in EGR2 knockout CD8+ CAR-T cells compared to AAVS1 knockout CAR T-cells. Libraries used in this enrichment analysis: A, Reactome 2016. B, NCI-Natu…
View article: Table S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Table S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Genes deferentially expressed in EGR2 compared to AAVS1 knockout CD8+ CAR T-cells. The corresponding log2 fold change values and statistical significance are provided for the listed genes.
View article: Table S1 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Table S1 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Genes comprising the TCF7 regulon, the type I IFN signature, and the EGR2 Co-expression signatures. Gene names and symbols are listed.
View article: Figure S3 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction
Figure S3 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction Open
Impact of EGR2 knockout on different T-cell subsets and CD28-based CAR T-cells. A, Naive, central memory, effector memory, and effector T-cells were magnetically isolated. PSMA CAR-T cells with AAVS1 and EGR2 knockout (KO) were then genera…
View article: TET2 regulates early and late transitions in exhausted CD8<sup>+</sup>T-cell differentiation and limits CAR T-cell function
TET2 regulates early and late transitions in exhausted CD8<sup>+</sup>T-cell differentiation and limits CAR T-cell function Open
CD8 + T-cell exhaustion hampers disease control in cancer and chronic infections and limits efficacy of T-cell−based therapies, such as CAR T-cells. Epigenetic reprogramming of CAR T-cells by targeting TET2, a methylcytosine dioxygenase th…