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Published on: February 5, 2020
Histologic and immune characterization of cutaneous immune-related adverse events induced by immune checkpoint
Omar Pacha1, Anisha B Patel2, Jonathan L Curry3
1Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA opacha@mdanderson.org.
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.
Insights
Immune checkpoint inhibitors (ICIs) can cause skin issues called cutaneous immune-related adverse events (CirAEs). Research shows THY1 (CD90) and M2 macrophages are elevated in CirAE lesions, suggesting their role in these toxic effects.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Immune checkpoint inhibitors (ICIs) are effective cancer treatments.
- Cutaneous immune-related adverse events (CirAEs) are common side effects of ICIs.
- The precise mechanisms driving CirAEs are not fully understood.
Purpose of the Study:
- To investigate the underlying mechanisms and histology of CirAEs.
- To characterize the immune markers present in CirAE lesions.
Main Methods:
- Prospective study of 15 advanced cancer patients treated with ICIs who developed CirAEs.
- Clinical and histological analysis of CirAE biopsy specimens.
- RNA expression assay to identify immune markers in lesions versus unaffected skin.
Main Results:
- CirAE lesions showed significantly upregulated THY1 (CD90) compared to unaffected skin.
- Increased M2 macrophages were observed in CirAE lesions.
- Histological analysis revealed diverse patterns including spongiotic, lichenoid, and interface dermatitis.
Conclusions:
- CirAEs exhibit varied histological patterns that can resemble autoimmune skin diseases.
- Upregulation of THY1 and elevated M2 macrophages suggest their involvement in CirAE pathogenesis.
- Further research is needed to understand the molecular basis of CirAEs and develop targeted therapies.
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