{
  "abstract": "Background Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.Methods Attempting to better understand their mechanisms and histology we conducted a prospective study of 15 patients with advanced cancers treated with ICIs who developed grade 2 or higher CirAEs. Clinical and histologic characterization of biopsy specimens of CirAEs was performed. Histologic analysis of patient biopsy specimens were subdivided by epidermal reaction patterns that included spongiotic, lichenoid, and interface dermatitis patterns. A targeted RNA expression assay was used to identify immune markers in CirAE lesions and adjacent unaffected skin samples.Conclusions Compared with adjacent unaffected skin, CirAE lesions had significantly upregulated THY1 (CD90) and increased M2 macrophages (adjusted p<0.05). Our findings suggest that CirAEs exhibit diverse histologic patterns that may mimic autoimmune skin diseases. The lack of distinct biomarker signatures may indicate complex and heterogeneous mechanisms underlying CirAEs; however, the upregulation of THY1 and elevated numbers of M2 macrophages in CirAE lesions suggest THY1 and M2 macrophages may be involved in the pathogenesis of these toxic effects. Further investigation to elucidate the molecular determinants of CirAEs and develop targeted therapeutic strategies is warranted.",
  "authors": [
    {
      "affiliations": [
        "Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Omar Pacha"
    },
    {
      "affiliations": [
        "Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Anisha B Patel"
    },
    {
      "affiliations": [
        "Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Jonathan L Curry"
    },
    {
      "affiliations": [
        "Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Cara L Haymaker"
    },
    {
      "affiliations": [
        "Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Nejla Ozirmak Lermi"
    },
    {
      "affiliations": [
        "Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Dzifa Yawa Duose"
    },
    {
      "affiliations": [
        "Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Ken Chen"
    },
    {
      "affiliations": [
        "Section of Immunology, Department of Allergy & Rheumatology, Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas, USA"
      ],
      "name": "Joud Hajjar"
    },
    {
      "affiliations": [
        "Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Aung Naing"
    }
  ],
  "title": "Histologic and immune characterization of cutaneous immune-related adverse events induced by immune checkpoint inhibitors",
  "uid": "bbb34897-6f52-5044-a7cf-8f01ee27f4d2"
}