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T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [BCR and TCR scRNA-Seq]

ABSTRACT: T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [BCR and TCR scRNA-Seq]

PROVIDER: PRJNA781605 | ENA |

REPOSITORIES: ENA

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T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [BCR and TCR scRNA-Seq]

Project description:Severe immune-related adverse events (irAEs) occur in up to 60% of melanoma patients treated with immune checkpoint inhibitors (ICIs). However, it remains unknown whether a common baseline immunological state precedes irAE development. Leveraging CyTOF, single-cell RNA sequencing, bulk RNA sequencing, and T cell receptor sequencing to analyze pretreatment blood from metastatic melanoma patients treated with ICIs, we investigated cellular factors associated with severe irAE development regardless of organ system involvement. Our results demonstrate circulating T cell characteristics associated with ICI-induced toxicity, with implications for improved diagnostics and clinical management.

2022-01-13 | GSE189126 | GEO

BCR, not TCR, repertoire diversity is associated with favorable COVID-19 [BCR-Seq]

Project description:The SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients. In this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages. The study included three unvaccinated patients from each outcome category. Although expanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, they represented only a small fraction of the total repertoire in all patients. In contrast, while deceased patients exhibited monoclonal B cell receptor (BCR) expansions without COVID-19 specificity, survivors demonstrated diverse and specific BCR clones. These findings suggest that neither TCR diversity nor BCR monoclonal expansions are sufficient for viral clearance and subsequent recovery. Differential gene expression analysis revealed that protein biosynthetic processes were enriched in survivors, but that potentially damaging mitochondrial ATP metabolism was activated in the deceased. This study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19.

2024-11-26 | GSE267642 | GEO

BCR, not TCR, repertoire diversity is associated with favorable COVID-19 [TCR-Seq]

2024-11-26 | GSE267639 | GEO

T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma

Project description:T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma

| PRJNA772729 | ENA

BCR, not TCR, repertoire diversity is associated with favorable COVID-19 [GEX]

2024-11-26 | GSE267645 | GEO

T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [scRNA-Seq]

Project description:T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [scRNA-Seq]

| PRJNA781606 | ENA

T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [scRNA-Seq]

2022-01-13 | GSE189125 | GEO

T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [bulk RNA-seq]

2022-01-13 | GSE186143 | GEO

T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [bulk RNA-seq]

Project description:T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [bulk RNA-seq]

| PRJNA772733 | ENA

Morphologic and molecular analysis of liver injury after SARS-CoV-2 vaccination reveals distinct characteristics [TCR-seq, BCR-seq]

Project description:Background and Aims: Liver injury after COVID-19 vaccination is very rare and shows clinical and histomorphological similarities with autoimmune hepatitis (AIH). Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI) and its relationship to AIH. Therefore, we compared VILI with AIH. Methods: Formalin-fixed and paraffin-embedded liver biopsy samples from patients with VILI (n=6) and from patients with an initial diagnosis of AIH (n=9) were included. Both cohorts were compared by histomorphological evaluation, whole-transcriptome and spatial transcriptome sequencing, multiplex immunofluorescence and immune repertoire sequencing. Results: Histomorphology was similar in both cohorts but showed more pronounced centrilobular necrosis in VILI. Gene expression profiling showed that mitochondrial metabolism and oxidative stress-related pathways were more and interferon response pathways less enriched in VILI. Multiplex analysis revealed that inflammation in VILI was dominated by CD8+ effector T cells, similar to drug-induced autoimmune like hepatitis (DI-AILH). In contrast, AIH showed a dominance of CD4+ effector T cells and CD79a+ B and plasma cells. T-cell receptor (TCR) and B-cell receptor (BCR) sequencing showed that T- and B-cell clones were more dominant in VILI than in AIH. In addition, many T-cell clones detected in the liver were also found in the blood. Interestingly, analysis of TCR beta chain and Ig heavy chain variable-joining gene usage further showed that TRBV6-1, TRBV5-1, TRBV7-6 and IgHV1-24 genes are used differently in VILI than in AIH. Conclusions: Our analyses support that SARS-CoV-2 vaccination-induced liver injury is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. VILI may be a separate entity, which is distinct from AIH and more closely related to DI-AILH.

2023-06-12 | GSE229424 | GEO

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