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Study Description

Therapeutic immune checkpoint blockade has revolutionized oncology, but treatments are limited by immune-related adverse events, including checkpoint inhibitor colitis (irColitis). To define molecular drivers of irColitis, we profiled ~300,000 cells from the colonic mucosa and blood of 29 patients and controls. Patients with irColitis showed expanded mucosal Tregs (regulatory T cells), CD8 tissue-resident memory T cells expressing CXCL13 and Th17 gene programs, and recirculating ITGB2 CD8 T cells. Cytotoxic CD4 T cells, recirculating CD8 T cells, and endothelial cells expressing hypoxia gene programs were further expanded in colitis associated with anti-PD-1/CTLA-4 compared to in the presence of anti-PD-1 therapy. Luminal epithelial cells in irColitis patients expressed PCSK9, PD-L1, and interferon-induced signatures associated with apoptosis, increased cell turnover, and malabsorption.

Raw data files from both colon and PBMCs from irColitis patients and controls have been provided to dbGaP. Count matrices derived from raw RNA-Seq data will be available through GEO accession GSE206301.

  • Study Design:
    • Case-Control
  • Study Type:
    • Case-Control
    • RNA Sequencing
    • Single Cell Analysis
    • Transcriptome Analysis
  • Total number of consented subjects: 33
  • Subject Sample Telemetry Report (SSTR)
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Publicly Available Data
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Diseases/Traits Related to Study (MeSH terms)
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Study Attribution
  • Principal Investigator
    • Alexandra-Chloe Villani. Harvard Medical School/MGH, Boston, MA, USA.
  • Instructor in Medicine
    • Molly Thomas. Harvard Medical School/MGH, Boston, MA, USA.
  • Research fellow
    • Kamil Slowikowski. Harvard Medical School/MGH, Boston, MA, USA.
  • Bioinformatics Specialist
    • Neal Smith. Harvard Medical School/MGH, Boston, MA, USA.