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Profiling Immune-Independent Response to Immune Checkpoint Inhibitors on Stem Cell-derived Cardiac Organoids [scRNAseq_Mouse]

ABSTRACT: The use of antibody based immune-checkpoint inhibitors (ICIs) have been highly successful in clinical treatment of several cancers. Despite the compelling efficacy of these drugs with their high binding affinity, there is incomplete understanding of non-target interactions in vivo. In this regard, ICIs are also known to cause immune-related adverse events (iRAEs) arising from infiltration of immune cells in tissues such as the heart. Due to the frequency of ICI treatments, extended half-life and the late onset of cardiac events, concerns have been raised regarding potential direct interactions of ICIs with major cellular cell types of the heart. The direct effects of these drugs in patients are limited due to rare incidence, and difficulty in obtaining patient heart biopsies in the pre- or post-symptomatic phase. Therefore, in order to study both functional and molecular changes in vitro and in vivo, we utilized a human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), cardiac organoids (COs), and immunocompromised NOD/SCID mouse models.

ORGANISM(S): Mus musculus

PROVIDER: GSE300367 | GEO | 2026/02/09

REPOSITORIES: GEO

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Profiling Immune-Independent Response to Immune Checkpoint Inhibitors on Stem Cell-derived Cardiac Organoids

Project description:The use of antibody based immune-checkpoint inhibitors (ICIs) have been highly successful in clinical treatment of several cancers. Despite the compelling efficacy of these drugs with their high binding affinity, there is incomplete understanding of non-target interactions in vivo. In this regard, ICIs are also known to cause immune-related adverse events (iRAEs) arising from infiltration of immune cells in tissues such as the heart. Due to the frequency of ICI treatments, extended half-life and the late onset of cardiac events, concerns have been raised regarding potential direct interactions of ICIs with major cellular cell types of the heart. The direct effects of these drugs in patients are limited due to rare incidence, and difficulty in obtaining patient heart biopsies in the pre- or post-symptomatic phase. Therefore, in order to study both functional and molecular changes in vitro, here we utilized a human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and multicellular cardiac organoids (COs).

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Profiling Immune-Independent Response to Immune Checkpoint Inhibitors on Stem Cell-derived Cardiac Organoids [scRNA-seq]

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Immune checkpoint blockade unleashes aberrant immune responses against the microbiota

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

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

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

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2024-06-22 | GSE228597 | GEO

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2020-11-01 | E-MTAB-8867 | biostudies-arrayexpress

T cells and monocyte-derived myeloid cells mediate immunotherapy-related hepatitis in a mouse model

Project description:Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) which are more severe when ICIs are used in combination. A mouse model was developed to elucidate the molecular mechanisms of immune-related hepatitis, one of the common irAEs associated with ICIs. Molecular profiling by single cell RNA sequencing was performed on Pdcd1-/- mice treated with anti-CTLA4 and/or the IDO1 inhibitor epacadostat or a 4-1BB agonistic antibody. ICI combination-induced hepatitis and 4-1BB agonist-mediated hepatitis share similar features yet maintain distinct immune signatures. Both were characterized by an expansion of activated T cells. Single-cell transcriptomics revealed that the hepatitis induced by combination ICIs is associated with a robust immune activation signature in all subtypes of T cells and T helper 1 skewing. Expression profiling revealed a central role for IFNγ and liver monocyte-derived macrophages in promoting a pro-inflammatory T-cell response to ICI combination and 4-1BB agonism.

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