AML induces TTCR-C4 NK-like transcriptional skewing associated with low persistence and dysfunction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1202029 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR33186158_1.fastq.gz | Fastqsanger.gz | |||
| SRR33186158_2.fastq.gz | Fastqsanger.gz | |||
| SRR33186159_1.fastq.gz | Fastqsanger.gz | |||
| SRR33186159_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 11 |
Similar Datasets
Project description:This dataset includes single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data generated to investigate T cell responses in the context of acute myeloid leukemia (AML) and WT1-specific TCR-T cell therapy. The scRNA-seq dataset comprises peripheral blood (PB) and bone marrow (BM) samples from AML patients treated with WT1-specific TCR-engineered T cells (TCR-T). We specifically profiled both endogenous CD8⁺ T cells and TCR-T cells to characterize their transcriptional states and assess the impact of AML on T cell differentiation and function. In-depth analysis of samples from a patient with a durable clinical response provided insights into the transcriptional profiles of TCR-T cells over time, including after Azacitidine treatment. The bulk RNA-seq dataset was generated using an in vitro model of AML-induced T cell dysfunction. CD8⁺ transgenic WT1-specific T cells (TTCR37-45) recognizing the HLA-A0201-restricted WT137-45 epitope were repeatedly challenged with WT1-expressing HLA-A0201-transduced K562 AML cells. Loss of tumor control by day 13 was associated with a transition from a naïve/stem-like transcriptional state to one enriched in effector, activation/exhaustion, and NK-like/Temra gene signatures. By day 23, activation/exhaustion markers declined while NK-like/Temra-associated genes persisted or increased, highlighting a phenotypic shift in dysfunctional T cells.
2025-04-16 | GSE285214 | GEO
Project description:CD56neg CD16+ Natural Killer (NK) cells have been reported to expand in chronic diseases and acute myeloid leukemia (AML). However, their biological role is still unclear. Using bulk RNA-sequencing, we compared gene expression profile of CD56neg CD16+ NK cells with conventional CD56bright, CD56dim CD16- and CD56dim CD16+ NK cells from blood samples of HV and AML patients. RNA-seq unveiled that CD56neg CD16+ NK cells were mature circulating NK cells with functional capacities. Taken together, our results suggest that CD56neg CD16+ NK cells are a relevant target for future NK-cell-based immunotherapies.
2024-12-20 | E-MTAB-14569 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications. 5 normal AML cells were compared with 8 NK deficient AML cells.
2015-07-24 | E-GEOD-50928 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications. Gene expression analysis were performed on CD56bright and CD56dim NK cells sorted from patients with impaired or normal CD56bright NK cells (n=2 for each patients? group) and from 3 HC
2015-07-24 | E-GEOD-34885 | biostudies-arrayexpress
Project description:Natural killer (NK) cells are critical for the immune response to cancer. However, solid tumor-infiltrating NK cells display reduced persistence and effector functions, limiting their clinical efficacy. To understand the mechanisms that induce human NK cell dysfunction in solid tumors, we compared single-cell gene expression in patient-matched tumor-infiltrating compared to tumor-adjacent NK cells to identify unfolded protein response (UPR) genes associated with worse cancer patient survival. Primary human NK cells accumulated unfolded proteins and induced a chronic UPR response to nutrient stress from the tumor microenvironment metabolome (TMM), sufficient to cause pronounced dysfunction and decreased persistence. Mechanistically, the transcription factor Fli1 epigenetically repressed UPR genes to limit human NK cell proteostasis in the presence of the TMM. CRISPR-mediated Fli1 deletion enhanced unfolded protein clearance, persistence, and tumor control in vivo. Thus, our results suggest that the TMM is sufficient to induce human NK cell dysfunction in solid tumors through the regulation of proteostasis.
2026-02-10 | GSE296351 | GEO
Project description:Natural killer (NK) cells are critical for the immune response to cancer. However, solid tumor-infiltrating NK cells display reduced persistence and effector functions, limiting their clinical efficacy. To understand the mechanisms that induce human NK cell dysfunction in solid tumors, we compared single-cell gene expression in patient-matched tumor-infiltrating compared to tumor-adjacent NK cells to identify unfolded protein response (UPR) genes associated with worse cancer patient survival. Primary human NK cells accumulated unfolded proteins and induced a chronic UPR response to nutrient stress from the tumor microenvironment metabolome (TMM), sufficient to cause pronounced dysfunction and decreased persistence. Mechanistically, the transcription factor Fli1 epigenetically repressed UPR genes to limit human NK cell proteostasis in the presence of the TMM. CRISPR-mediated Fli1 deletion enhanced unfolded protein clearance, persistence, and tumor control in vivo. Thus, our results suggest that the TMM is sufficient to induce human NK cell dysfunction in solid tumors through the regulation of proteostasis.
2026-02-10 | GSE296350 | GEO
Project description:Natural killer (NK) cells are critical for the immune response to cancer. However, solid tumor-infiltrating NK cells display reduced persistence and effector functions, limiting their clinical efficacy. To understand the mechanisms that induce Mouse NK cell dysfunction in solid tumors, we compared single-cell gene expression in patient-matched tumor-infiltrating compared to tumor-adjacent NK cells to identify unfolded protein response (UPR) genes associated with worse cancer patient survival. Primary Mouse NK cells accumulated unfolded proteins and induced a chronic UPR response to nutrient stress from the tumor microenvironment metabolome (TMM), sufficient to cause pronounced dysfunction and decreased persistence. Mechanistically, the transcription factor Fli1 epigenetically repressed UPR genes to limit Mouse NK cell proteostasis in the presence of the TMM. CRISPR-mediated Fli1 deletion enhanced unfolded protein clearance, persistence, and tumor control in vivo. Thus, our results suggest that the TMM is sufficient to induce Mouse NK cell dysfunction in solid tumors through the regulation of proteostasis.
2026-02-10 | GSE296356 | GEO
Project description:Natural killer (NK) cells are critical for the immune response to cancer. However, solid tumor-infiltrating NK cells display reduced persistence and effector functions, limiting their clinical efficacy. To understand the mechanisms that induce human NK cell dysfunction in solid tumors, we compared single-cell gene expression in patient-matched tumor-infiltrating compared to tumor-adjacent NK cells to identify unfolded protein response (UPR) genes associated with worse cancer patient survival. Primary human NK cells accumulated unfolded proteins and induced a chronic UPR response to nutrient stress from the tumor microenvironment metabolome (TMM), sufficient to cause pronounced dysfunction and decreased persistence. Mechanistically, the transcription factor Fli1 epigenetically repressed UPR genes to limit human NK cell proteostasis in the presence of the TMM. CRISPR-mediated Fli1 deletion enhanced unfolded protein clearance, persistence, and tumor control in vivo. Thus, our results suggest that the TMM is sufficient to induce human NK cell dysfunction in solid tumors through the regulation of proteostasis.
2026-02-10 | GSE296352 | GEO
Project description:Natural killer (NK) cells are critical for the immune response to cancer. However, solid tumor-infiltrating NK cells display reduced persistence and effector functions, limiting their clinical efficacy. To understand the mechanisms that induce human NK cell dysfunction in solid tumors, we compared single-cell gene expression in patient-matched tumor-infiltrating compared to tumor-adjacent NK cells to identify unfolded protein response (UPR) genes associated with worse cancer patient survival. Primary human NK cells accumulated unfolded proteins and induced a chronic UPR response to nutrient stress from the tumor microenvironment metabolome (TMM), sufficient to cause pronounced dysfunction and decreased persistence. Mechanistically, the transcription factor Fli1 epigenetically repressed UPR genes to limit human NK cell proteostasis in the presence of the TMM. CRISPR-mediated Fli1 deletion enhanced unfolded protein clearance, persistence, and tumor control in vivo. Thus, our results suggest that the TMM is sufficient to induce human NK cell dysfunction in solid tumors through the regulation of proteostasis.
2026-02-10 | GSE296355 | GEO
Project description:Natural killer (NK) cells are critical for the immune response to cancer. However, solid tumor-infiltrating NK cells display reduced persistence and effector functions, limiting their clinical efficacy. To understand the mechanisms that induce Mouse NK cell dysfunction in solid tumors, we compared single-cell gene expression in patient-matched tumor-infiltrating compared to tumor-adjacent NK cells to identify unfolded protein response (UPR) genes associated with worse cancer patient survival. Primary Mouse NK cells accumulated unfolded proteins and induced a chronic UPR response to nutrient stress from the tumor microenvironment metabolome (TMM), sufficient to cause pronounced dysfunction and decreased persistence. Mechanistically, the transcription factor Fli1 epigenetically repressed UPR genes to limit Mouse NK cell proteostasis in the presence of the TMM. CRISPR-mediated Fli1 deletion enhanced unfolded protein clearance, persistence, and tumor control in vivo. Thus, our results suggest that the TMM is sufficient to induce Mouse NK cell dysfunction in solid tumors through the regulation of proteostasis.
2026-02-10 | GSE296354 | GEO