Histologic and immune characterization of cutaneous immune-related adverse events induced by immune checkpoint inhibitors

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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 pTHY1 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.
Funding Information
  • University of Texas MD Anderson Cancer Center (Institutional Research Grant)

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