Immune Profiling of Dermatologic Adverse Events from Checkpoint Blockade using Tissue Cyclic Immunofluorescence: A Pilot Study

By inhibiting key immunomodulatory pathways, immune checkpoint inhibitors (ICIs) can profoundly improve survival in cancer patients. However, dermatologic adverse events (dAEs) are frequently observed in patients on ICI therapy (35-50%) ( Kato et al., 2019 Kato K. Cho B.C. Takahashi M. Okada M. Lin C.Y. Chin K. et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. The Lancet Oncology. 2019; 20 (Elsevier Ltd): 1506-1517 Abstract Full Text Full Text PDF PubMed Scopus (687) Google Scholar ; Patel and Pacha, 2018 Patel AB, Pacha O. Skin Reactions to Immune Checkpoint Inhibitors BT - Immunotherapy. In: Naing A, Hajjar J, editors. Cham: Springer International Publishing; 2018. p. 117–129 Google Scholar ). DAEs are characterized by diverse reaction patterns, visible clinical specificity, and easily accessed tissues, but deep phenotyping of skin immune toxicity is limited. Histological phenotyping primarily involves immunohistochemistry (IHC), in which serial tissue sections are scored by a pathologist on a simple numerical scale (0-4). This approach can be effective for diagnosis or prognosis but does not provide the in-depth single-cell data necessary to precisely subtype immune cells and characterize mechanisms of activation and engagement with epithelial cells ( Shi et al., 2016 Shi V.J. Rodic N. Gettinger S. Leventhal J.S. Neckman J.P. Girardi M. et al. Clinical and Histologic Features of Lichenoid Mucocutaneous Eruptions Due to Anti–Programmed Cell Death 1 and Anti–Programmed Cell Death Ligand 1 Immunotherapy. JAMA Dermatology. 2016; 152: 1128-1136 Crossref PubMed Scopus (184) Google Scholar ).