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Expression of CD94 and CD96 on CD8+ T cells early after allogeneic stem cell transplantation is predictive of subsequent disease relapse and survival

ABSTRACT: Expression of CD94 and CD96 on CD8+ T cells early after allogeneic stem cell transplantation is predictive of subsequent disease relapse and survival

PROVIDER: PRJNA769281 | ENA |

REPOSITORIES: ENA

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Expression of CD94 and CD96 on CD8+ T cells early after allogeneic stem cell transplantation is predictive of subsequent disease relapse and survival

Project description:Allogeneic stem cell transplantation is used widely in the treatment of hematopoietic malignancy. However relapse of malignant disease is the primary cause of treatment failure and reflects loss of the immunological graft versus leukaemia effect. We studied the transcriptional and phenotypic profile of CD8+ T cells in the first month following transplantation and related this to risk of subsequent relapse. Single cell transcriptional profiling identified 5 discrete CD8+ T cell clusters. High levels of T cell activation and acquisition of a regulatory transcriptome were apparent in patients who went on to suffer disease relapse. A relapse-associated gene signature of 39 genes was then assessed in a confirmation cohort of 34 patients. High level expression of the inhibitory receptor CD94/NKG2A on CD8+ T cells within the first month was associated with 4.8 fold increased risk of relapse and 2.7 fold reduction in survival over the subsequent 4 years. Furthermore, reduced expression of the activatory molecule CD96 was associated with 2.2 fold increased risk of relapse and 1.9 fold reduction in survival. This work identifies CD94 and CD96 as potential targets for CD8-directed immunotherapy in the very early phase following allogeneic transplantation with the potential to reduce long term relapse rates and improve patient survival.

2022-07-31 | GSE185498 | GEO

CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell comparison

Project description:CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell comparison

| PRJNA504633 | ENA

CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell chromatin histone modification assay

Project description:CUT and RUN was performed for 3 NK populations and found CD94+CD56hi NK cells exhibit unique H3K4me1, H3K4me4 enriched region, we also identified TCF7 binding region in CD94+CD56hi NK cells.

2019-12-10 | GSE122549 | GEO

CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell comparison

Project description:We compared transcriptomes of 3 NK populations and found CD94+CD56hi NK cells exhibit unique transcriptome.

2019-12-10 | GSE122324 | GEO

Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation

Project description:Administration of azithromycin after allogeneic hematopoietic stem cell transplantation for hematological malignancies has been associated with relapse in a randomized phase 3 controlled clinical trial. Studying 240 samples from patients randomized in this trial is a unique opportunity to better understand the mechanisms underlying relapse, the first cause of mortality after transplantation. We used multi-omics on patients' samples to decipher immune alterations associated with azithromycin intake and post-transplant relapsed malignancies. Azithromycin was associated with a network of altered energy metabolism pathways and immune subsets, including T cells biased toward immunomodulatory and exhausted profiles. In vitro, azithromycin exposure inhibited T cells cytotoxicity against tumor cells and impaired T cells metabolism through glycolysis inhibition, mitochondrial genes downregulation, and immunomodulatory genes upregulation, notably SOCS1. These results highlight that azithromycin directly affects immune cells that favor relapse, which raises caution about long-term use of azithromycin treatment in patients at high risk of malignancies.

2022-08-22 | MTBLS406 | MetaboLights

CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell chromatin accessibility assay

Project description:CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell chromatin accessibility assay

| PRJNA505524 | ENA

CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell chromatin accessibility assay

Project description:ATAC-Seq was performed for 3 NK populations and found CD94+CD56hi NK cells exhibit unique chromatin accessible region

2019-12-10 | GSE122548 | GEO

CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell chromatin histone modification assay

Project description:CD94-CD56dim, CD94+CD56dim and CD94+CD56hi natural killer (NK) cell chromatin histone modification assay

| PRJNA505525 | ENA

Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation

Project description:Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation

| PRJNA947751 | ENA

Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation

Project description:Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation

| PRJNA947752 | ENA

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