Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CUT&RUN profiling of EZH2, H3K27me3, and H3K4me3 enrichment in FACS-sorted CD70⁻ and CD70⁺ tumor cells from untreated ex vivo ccRCC and HGSOC patient-derived xenografts.

ABSTRACT: CD70 expression in solid tumors is heterogeneous. We demonstrate that cells appearing CD70-negative retain ultra-low levels of CD70 expression. These cells that appear negative by conventional detection methods. Bulk ATAC-seq analysis of FACS-sorted CD70⁻ and CD70⁺ tumor populations revealed differential chromatin accessibility, indicating epigenetic regulation of CD70 expression in both ccRCC and HGSOC models. CUT&RUN profiling of EZH2, H3K27me3, and H3K4me3 in FACS-sorted CD70⁻ and CD70⁺ tumor cells derived from ccRCC and HGSOC PDXs revealed enrichment of differential repressive and activating histone modifications.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311098 | GEO | 2026/02/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Sensitive CAR T cells redefine targetable CD70 expression in solid tumors [ATAC-seq]

Project description:CD70 expression in solid tumors is heterogeneous. We demonstrate that cells appearing CD70-negative retain ultra-low levels of CD70 expression. These cells that appear negative by conventional detection methods. Bulk ATAC-seq analysis of FACS-sorted CD70⁻ and CD70⁺ tumor populations revealed differential chromatin accessibility, indicating epigenetic regulation of CD70 expression in both ccRCC and HGSOC models.

2026-02-26 | GSE311096 | GEO

CUT&RUN profiling of EZH2, H3K27me3, and H3K4me3 enrichment in FACS-sorted CD70⁻ and CD70⁺ tumor cells from untreated ex vivo ccRCC and HGSOC patient-derived xenografts.

Project description:CUT&RUN profiling of EZH2, H3K27me3, and H3K4me3 enrichment in FACS-sorted CD70⁻ and CD70⁺ tumor cells from untreated ex vivo ccRCC and HGSOC patient-derived xenografts.

| PRJNA1368670 | ENA

Analysis of CD70 wild type or CD70 knock out CD70-specific nanoCAR T cells

Project description:CD70 is an attractive target for chimeric antigen receptor (CAR) T cell therapy as treatment for both solid and liquid malignancies. However, functionality of CD70-specific CAR T cells is only modest. Here, we optimized a CD70-specific VHH based CAR (nanoCAR). We evaluated the nanoCARs in clinically relevant models in vitro, using co-cultures of CD70-specific nanoCAR T cells with malignant rhabdoid tumor organoids, and in vivo by using a diffuse large B cell lymphoma (DLBCL) patient-derived xenograft (PDX) model. Whereas the nanoCAR T cells were highly efficient in organoid co-cultures, they showed only modest efficacy in the PDX model. Knocking out CD70 expression in the nanoCAR T cells resulted in dramatically enhanced functionality in the PDX model, suggesting that CD70 interaction in cis with the nanoCAR induces exhaustion. Through single-cell transcriptomics, we obtained evidence that CD70 KO CD70-specific nanoCAR T cells are protected from antigen-induced exhaustion. Our data show that CARs targeted to endogenous T cell antigens, negatively affect CAR T cell functionality by inducing an exhausted state, which can be overcome by knocking out the specific target, in this case CD70.

2024-06-17 | GSE227435 | GEO

Analysis of CD70 wild type or CD70 knock out CD70-specific nanoCAR T cells [RNA-Seq]

Project description:CD70 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy for the treatment of both solid and liquid malignancies. However, the functionality of CD70-specific CAR T-cells is modest. We optimized a CD70-specific VHH-based CAR (nanoCAR). We evaluated the nanoCARs in clinically relevant models in vitro, using co-cultures of CD70-specific nanoCAR T-cells with malignant rhabdoid tumor organoids, and in vivo using a diffuse large B-cell lymphoma (DLBCL) patient-derived xenograft (PDX) model. Whereas the nanoCAR T-cells were highly efficient in organoid co-cultures, they showed only modest efficacy in the PDX model. Fratricide was not causing this loss in efficacy but rather CD70 interaction in cis with the nanoCAR, as validated by imaging flowcytometry, induces exhaustion. Knocking out CD70 expression in nanoCAR T-cells using CRISPR/Cas9, resulted in dramatically enhanced functionality in the DLBCL PDX model. Through single-cell transcriptomics, we obtained evidence that CD70 knock out (KO) CD70-specific nanoCAR T-cells were protected from antigen-induced exhaustion. In addition, we were able to demonstrate that WT CD70-specific nanoCAR T-cells already exhibit signs of exhaustion shortly after production. Their gene signature strongly overlapped with gene signatures of exhausted CAR T-cells. On the other hand, the gene signature of KO nanoCAR T-cells overlapped with the gene signature of CAR T-cell infusion products that led to complete responses in chronic lymphatic leukemia patients. Our data show that CARs targeting endogenous T-cell antigens, negatively affect CAR T-cell functionality by inducing an exhausted state, which can be overcome by knocking out the specific target, in this case CD70.

2024-06-17 | GSE265937 | GEO

RNAseq data for HGSOC PH039 PDXs at baseline and treated with cycles of 100 mg/kg niraparib for 21 days for four treatment rounds

Project description:RNAseq data for HGSOC PH039 PDXs at baseline and treated with cycles of 100 mg/kg niraparib for 21 days for four treatment rounds.

2021-06-16 | GSE163854 | GEO

CD8α and CD70 mark human natural killer cell populations which differ in cytotoxicity

Project description:Natural Killer (NK) cells are innate immune cells that can directly detect and kill cancer cells. Understanding the molecular determinants regulating human NK cell cytotoxicity could help harness these cells for cancer therapies. To this end, we compared the transcriptome of NK cell clones derived from human peripheral blood, which were strongly or weakly cytotoxic against 721.221 and other target cells. After one month of culture, potent NK cell clones showed a significant upregulation in genes involved in cell cycle progression, suggesting that proliferating NK cells were particularly cytotoxic. Beyond two months of culture, NK cell clones which were strongly cytotoxic varied in their expression of 28 genes, including CD8Α and CD70; NK cells with high levels of CD70 expression were weakly cytotoxic while high CD8Α correlated with strong cytotoxicity. Thus, NK cells were cultured and sorted for expression of CD70 and CD8α, and in accordance with the transcriptomic data, CD70 + NK cells showed low cytotoxicity against 721.221 and K562 target cells. Cytotoxicity of CD70 + NK cells could be enhanced using blocking antibodies against CD70, indicating a direct role for CD70 in mediating low cytotoxicity. Furthermore, time-lapse microscopy of NK cell-target cell interactions revealed that CD8α + NK cells have an increased propensity to sequentially engage and kill multiple target cells. Thus, these two markers relate to NK cell populations which are capable of potent killing (CD70 -) or serial killing (CD8α + ).

2025-02-11 | GSE289212 | GEO

Analysis of CD70 wild type or CD70 knock out CD70-specific nanoCAR T cells

Project description:Analysis of CD70 wild type or CD70 knock out CD70-specific nanoCAR T cells

| PRJNA945042 | ENA

Sensitive CAR T cells redefine targetable CD70 expression in solid tumors [Multiomics]

Project description:Overcoming tumor antigen heterogeneity in solid tumors is a major challenge for cancer immunotherapies including chimeric antigen receptor (CAR) T cells. Unlike CD19 for B-cell malignancies, no target with pan-cellular expression in solid tumors and absence in normal vital cells has been identified. CD70 is a potential candidate, confined to immune cell subsets and aberrantly expressed in many solid tumors, albeit heterogeneously. We find that CD70 expression in heterogeneous tumors is not binary but ranges from high to very low, appearing negative. We show that CD70-heterogeneous tumors are efficiently eliminated by highly sensitive CD70 receptors where prototypic CAR T cells fail. We further identify an epigenetic signature that predicts targetable expression. These findings provide a potential strategy to treat a broad range of solid tumors.

2026-02-26 | GSE306275 | GEO

RNA sequencing analysis of ex vivo expanded CD27+CD70- and CD27-CD70+ human regulatory T cells

Project description:Our study shows that after extended stimulation of human CD4+CD25+CD127- Tregs in vitro, a stable cell subset that downregulates CD27 and upregulates CD70 develops. Expanded CD27+CD70- Tregs display a gene profile which closely relates to the previously described “Treg gene signature”, whereas CD27-CD70+ Tregs express some genes associated with Treg gene signature and some genes overexpressed in conventional T cells.

2020-07-10 | GSE129251 | GEO

Sensitive CAR T cells redefine targetable CD70 expression in solid tumors [CITE-seq]

2026-02-26 | GSE306608 | GEO