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Immune-related adverse events after immune checkpoint blockade-based therapy are associated with improved survival in advanced sarcoma

ABSTRACT: Immune-related adverse events after immune checkpoint blockade-based therapy are associated with improved survival in advanced sarcoma

PROVIDER: PRJNA962617 | ENA |

REPOSITORIES: ENA

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Project description:Immune-related adverse events after immune checkpoint blockade-based therapy are associated with improved survival in advanced sarcoma

| PRJNA962616 | ENA

Multiomics analysis of immune-related adverse events in melanoma patients treated with immune checkpoint inhibitors

Project description:Multiomics analysis of immune-related adverse events in melanoma patients treated with immune checkpoint inhibitors

| PRJNA942629 | ENA

Platelet proteomics profiling in transfusion adverse events

Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components SDA-PC (platelet pellets) involved in transfusion adverse events.

2019-02-13 | PXD008886 | Pride

Platelet proteomics profiling in transfusion adverse events, part 2

Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components PPC (platelet pellets) involved in transfusion adverse events.

2019-02-13 | PXD003510 | Pride

Multiomics analysis of immune-related adverse events in melanoma patients treated with immune checkpoint inhibitors

Project description:Immune checkpoint inhibitors (ICIs) are a standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events (irAEs). Proteomic analysis and multiplex cytokine/chemokine assay from serum at baseline and at irAEs onset in 82 patients indicated aberrant T-cell activity with differential expression of Type I and III immune signatures. This was in line with an increase in the proportions of monocytes and decrease of IL-17A producing CD4+ T-cells in the peripheral blood in single cell RNA sequencing. Multiplex immunohistochemistry on ICI-induced skin rash and inflamed colon showed increase in the proportion of CD4+ T-cells with IL-17A expression. Anti-IL17A antagonistic mAbs were administered in two patients with severe myocarditis, colitis and skin rash with resolution of the irAE. This study demonstrates the potential role of Type III CD4+ T-cells in the irAEs development and provides proof-of-principle evidence to support a clinical trial examining anti-IL17A in their management.

2023-12-01 | GSE227001 | GEO

Single cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors

Project description:Single cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors

| PRJNA892990 | ENA

Transcriptomic-based functional characterization of adverse events following lymphatic filariasis treatment

Project description:Transcriptomic-based functional characterization of adverse events following lymphatic filariasis treatment

| PRJNA432948 | ENA

Project description:The association between immune-related AEs (irAE) and outcome in patients with sarcoma is not known. We retrospectively reviewed a cohort of patients with advanced sarcoma treated with immune checkpoint blockade (ICB)-based therapy. Association of irAEs with survival was assessed using a Cox regression model that incorporated irAE occurrence as a time-dependent covariate. Tumor samples with available RNA sequencing data were stratified by presence of an irAE to identify patterns of differential gene expression. A total of 131 patients were included. Forty-two (32%) had at least one irAE of any grade and 16 (12%) had at least one grade ≥ 3 irAE. The most common irAEs were hypothyroidism (8.3%), arthralgias (5.3%), pneumonitis (4.6%), allergic reaction (3.8%), and elevated transaminases (3.8%). Median progression-free survival (PFS) and overall survival (OS) from the time of study entry were 11.4 [95% confidence interval (CI), 10.7-15.0) and 74.6 weeks (CI, 44.9-89.7), respectively. On Cox analysis adjusting for clinical covariates that were significant in the univariate setting, the HR for an irAE (HR, 0.662; CI, 0.421-1.041) approached, but did not reach statistical significance for PFS (P = 0.074). Patients had a significantly lower HR for OS (HR, 0.443; CI, 0.246-0.798; P = 0.007) compared with those without or before an irAE. Gene expression profiling on baseline tumor samples found that patients who had an irAE had higher numbers of tumor-infiltrating dendritic cells, CD8+ T cells, and regulatory T cells as well as upregulation of immune and inflammatory pathways.SignificanceirAE after ICB therapy was associated with an improved OS; it also approached statistical significance for improved PFS. Patients who had an irAE were more likely to have an inflamed tumor microenvironment at baseline.

| S-EPMC10583739 | biostudies-literature

Single cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors

Project description:PD-1 is an essential inhibitory receptor in T cells, and antibodies that block its interaction with its ligands can augment anti-tumor immune responses. The clinical potential of these agents is limited by the fact that approximately half of all patients who receive anti-PD-1 treatment subsequently develop immune-related Adverse Events (irAEs). To generate insights into the cellular and molecular changes that occur during anti-PD-1 treatment, and to discover predictive biomarkers of irAEs, we performed single cell RNA sequencing of circulating T cells collected from cancer patients who did and did not develop irAEs following PD-1 blockade. Using the K-nearest-neighbor-based network graph drawing layout, we show the involvement of unique gene expression signatures and subpopulations of T cells. We identified that at baseline, patients with arthritis had significantly less cells with features of CD8 TCM cells, patients with pneumonitis had more CD4 TH2 cells, and patients with thyroiditis had more CD4 TH17 cells, when compared to patients who did not develop irAEs. Moreover, T cell receptor sequencing revealed distinctive clonal expansion, and suggested involvement of organ-specific and potentially pathogenic T cell clones among patients with irAEs. Altogether, these data support the hypothesis that different populations of T cells are associated with different irAEs and that quantification and characterization of these populations of T cells pre-treatment could serve as a toxicity-specific, predictive biomarker.

2022-12-14 | GSE216329 | GEO

Inhibition of IL-17A Protects against Thyroid Immune-related Adverse Events while Preserving Checkpoint Inhibitor Anti-tumor Efficacy [RNA-seq (murine)]

Project description:Checkpoint inhibitor (ICI) immunotherapy leverages the body’s own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune related adverse events (IrAE) lead to treatment interruption, permanent organ dysfunction, hospitalization and premature death. Thyroiditis is one of the most common IrAE, but the cause of thyroid IrAE remains unknown. Here we present a novel mouse model in which checkpoint inhibitor therapy leads to multi-organ autoimmune infiltrates and show that activation and infiltration of Type 3 immune cells including IL17A+ RORgt+ CD4+ (T helper 17 or Th17) and gamma delta 17 (gdT17) T cells promote thyroid IrAE development. In parallel, Th17 and gdT17 cells were similarly expanded in cancer patients treated with ICI. Furthermore, antibody-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice. Finally, combination of IL-17A neutralization with ICI treatment in a mouse tumor model did not reduce ICI anti-tumor efficacy and indeed showed a trend toward enhancement. These studies suggest that targeting Th17 and gd17 function may reduce IrAE without impairing ICI anti-tumor efficacy and may be a generalizable strategy to address IL17-mediated IrAE.

2022-11-21 | GSE176561 | GEO

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