Project description:In this study we set investigate four aspects of irColitis that are vital to the pathogenesis of most immunotherapy related adverse events: (1) the interactions between CD8 T cells and other immune, epithelial, and mesenchymal cells that sustain organ specific inflammation; (2) the contribution of circulating immune cells to disease; (3) the epithelial and mesenchymal defects that define parenchymal organ injury and dysfunction; (4) the transcriptional features of colitis associated with anti-PD-1 monotherapy versus anti-PD-1/CTLA-4 dual therapy. We leveraged single-cell RNA-sequencing (scRNA-seq) and single-nuclei RNA-sequencing (snRNA-seq) of colon mucosal biopsies and paired blood specimens collected from a well-characterized cohort of irColitis cases and controls to define the cellular and molecular drivers of irColitis.

2024-02-10 | GSE206300 | GEO

Colitis associated with immune checkpoint inhibitors [tissue_cells]

2024-02-10 | GSE206299 | GEO

Colitis associated with immune checkpoint inhibitors [blood_cells]

2024-02-10 | GSE206298 | GEO

Transcriptomic profile comparison of an in vivo model of dual combination immune checkpoint colitis or monotherapy immune checkpoint colitis

Project description:Immune checkpoint inhibitors (CPIs) have revolutionised cancer treatment, with previously untreatable disease now amenable to potential cure. Combination regimens of anti-CTLA-4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. CPI-induced colitis is a common and serious complication. A higher proportion of patients undergoing monotherapy anti-CTLA-4 treatment tend to develop colitis compared to monotherapy treated anti-PD-1 treated patients. This effect is enhanced when patients are treated with both drugs. To probe the impact of either anti-CTLA4 or anti-PD1 on intestinal homeostasis, mice were challenged with anti-CTLA-4 and anti-PD-1 immunotherapy in either monotherapy or together in combination. Manipulation of the intestinal microbiota has also been shown to be important in both this model, from previous data, and in patients. Colonic immune responses were then profiled using bulk RNA-sequencing.

2023-09-08 | GSE241664 | GEO

Transcriptomic profile comparison of an in vivo model of dual combination immune checkpoint colitis or monotherapy immune checkpoint colitis

Project description:Transcriptomic profile comparison of an in vivo model of dual combination immune checkpoint colitis or monotherapy immune checkpoint colitis

| PRJNA1009062 | ENA

Transcriptomic profiling of an in vivo mouse model of immune checkpoint induced colitis

2023-09-08 | GSE222843 | GEO