GEO DataSets

(Submitter supplied) We hypothesized that there are distinct signatures in chromatin of circulating CD8+ T cells depending on their response to anti-PD-1 therapy due to their long-term interaction with the internal stimuli, such as with tumor and its microenvironment, and external stimuli, such as with infectious diseases. To identify unique chromatin regions predicting the clinical outcome of PD-1 therapy, we performed an assay for transposase-accessible chromatin sequencing (ATAC-seq) using blood samples of patients enrolled in PD-1 therapy. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

32 Samples

Download data: BW

(Submitter supplied) The goal of this study was to identify the molecular programming using ATAC-seq of CD8 T cells responding to different viral infections. Mice were infected with either LCMV Armstrong to model an acute infection or LCMV Clone-13 to model a chronic infection. At various time points following infection, virus-specific CD8 T cells were purified and ATAC-seq performed. These data identify the changes in chromatin accessibility associated with acute infections and the establishment of functional memory versus those accessibility changes associated with chronic infection.

Organism:

Mus musculus

Type:

Other

Platform:

GPL17021

17 Samples

Download data: BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

29 Samples

Download data: BW, TXT

(Submitter supplied) T cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8+ tumor-infiltrating lymphocytes (TIL) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, non-exhausted, TIL and in acutely restimulated CD8+ T cells, we define a pattern of chromatin accessibility specific for T cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors. Anti-PD-L1 treatment of tumor-bearing mice results in cessation of tumor growth and partial rescue of cytokine production by the dysfunctional TIL, with only limited changes in gene expression and chromatin accessibility. Our studies provide a valuable resource for the molecular understanding of T cell exhaustion in cancer and other inflammatory settings.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

10 Samples

Download data: BW

(Submitter supplied) T cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8+ tumor-infiltrating lymphocytes (TIL) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, non-exhausted, TIL and in acutely restimulated CD8+ T cells, we define a pattern of chromatin accessibility specific for T cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors. Anti-PD-L1 treatment of tumor-bearing mice results in cessation of tumor growth and partial rescue of cytokine production by the dysfunctional TIL, with only limited changes in gene expression and chromatin accessibility. Our studies provide a valuable resource for the molecular understanding of T cell exhaustion in cancer and other inflammatory settings.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

5 Samples

Download data: TXT

(Submitter supplied) T cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8+ tumor-infiltrating lymphocytes (TIL) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, non-exhausted, TIL and in acutely restimulated CD8+ T cells, we define a pattern of chromatin accessibility specific for T cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors. Anti-PD-L1 treatment of tumor-bearing mice results in cessation of tumor growth and partial rescue of cytokine production by the dysfunctional TIL, with only limited changes in gene expression and chromatin accessibility. Our studies provide a valuable resource for the molecular understanding of T cell exhaustion in cancer and other inflammatory settings.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

8 Samples

Download data: TXT

(Submitter supplied) T cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8+ tumor-infiltrating lymphocytes (TIL) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, non-exhausted, TIL and in acutely restimulated CD8+ T cells, we define a pattern of chromatin accessibility specific for T cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors. Anti-PD-L1 treatment of tumor-bearing mice results in cessation of tumor growth and partial rescue of cytokine production by the dysfunctional TIL, with only limited changes in gene expression and chromatin accessibility. Our studies provide a valuable resource for the molecular understanding of T cell exhaustion in cancer and other inflammatory settings.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: BW

(Submitter supplied) In response to acute infection, naive CD8+ T cells expand, differentiate into effector cells and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8+ T cells acquire an “exhausted” phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8+ T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq. more...

Organism:

Mus musculus

Type:

Other; Expression profiling by high throughput sequencing

Platform:

GPL17021

44 Samples

Download data: TSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: MTX, TSV, TXT

(Submitter supplied) Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using 89Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8+ T cells and CD11b+ myeloid cells in response to anti-PD-1 treatment in the MC38 colorectal mouse adenocarcinoma model. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

2 Samples

Download data: MTX, TSV

(Submitter supplied) Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using 89Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8+ T cells and CD11b+ myeloid cells in response to anti-PD-1 treatment in the MC38 colorectal mouse adenocarcinoma model. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

4 Samples

Download data: TXT

(Submitter supplied) The programmed cell death protein 1 (PD-1) limits effector T-cell functions in peripheral tissues and its inhibition leads to clinical benefit in different cancers. To better understand how PD-1 blockade therapy modulates the tumor-host interactions, we evaluated three syngeneic murine tumor models, the BRAFV600E-driven YUMM1.1 and YUMM2.1 melanomas, and the carcinogen-induced murine colon adenocarcinoma MC38. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

3 Samples

Download data: XLSX

(Submitter supplied) Background: Binding of the programmed death-1 (PD-1) receptor to its ligands (PD-L1/2) transduces inhibitory signals that promote exhaustion of activated T cells. Blockade of the PD 1 pathway is widely used for cancer treatment, yet the inhibitory signals transduced by PD-1 in T cells remain elusive. Methods: Expression profiles of human CD8+ T cells in resting, activated (CD3+CD28) and PD-1-stimulated cells (CD3+CD28+PD-L1-Fc) conditions were evaluated by RNA-seq. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

21 Samples

Download data: TXT

(Submitter supplied) We compared the transcriptom between respondrs and non-responders before and after PD-1 blockade therapy in melanoma patients, and defined their difference in context of T cell function.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL21103 GPL13112

4 Samples

Download data: TXT

(Submitter supplied) An improved understanding of the anti-tumor CD8+ T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8+ tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8+ TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1? TILs. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL19057 GPL17021

28 Samples

Download data: TXT

(Submitter supplied) RNA-Seq analysis was used to study the profile of CD8 t cells from melanoma patients before and after treatment to understand if we can detect transcriptional changes in peripheral blood

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL23177

13 Samples

Download data: TXT