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Immunotherapy‐induced sarcoidosis in patients with melanoma treated with PD ‐1 checkpoint inhibitors: Case series and immunophenotypic analysis
Author(s) -
Lomax Anna J.,
McGuire Helen M.,
McNeil Catriona,
Choi Clara J.,
Hersey Peter,
Karikios Deme,
Shan Kerwin,
Hal Sebastian,
Carr Urszula,
Crotty Anne,
Gupta Sandeep K.,
Hollingsworth Jane,
Kim Haewon,
Fazekas de St Groth Barbara,
McGill Neil
Publication year - 2017
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13076
Subject(s) - medicine , sarcoidosis , melanoma , immunotherapy , ipilimumab , biopsy , immunology , oncology , dermatology , cancer research , immune system
Abstract Aim Sarcoidosis is a multisystem granulomatous disease. This condition has a documented association with the diagnosis of melanoma and can be induced in melanoma patients receiving anti‐neoplastic therapy. We evaluated a case series of melanoma patients who developed immunotherapy‐induced sarcoidosis. Methods Three patients with melanoma ( n = 1 resected Stage III , n = 2 metastatic) treated with anti‐programmed cell death ( PD )‐1 antibody therapy at two institutions developed biopsy‐proven sarcoidosis. We used mass cytometry to determine expression of the relevant chemokine receptors ( CR ) by peripheral blood mononuclear cells for two of the three patients who developed sarcoidosis and 13 melanoma patients who did not. Blood samples were collected before receiving PD ‐1 checkpoint inhibitor therapy. Results Immunophenotypic analysis demonstrated abnormally high numbers of circulating Th17.1 ( CCR 6 + CCR 4 − CXCR 3 + CCR 10 − ) cells prior to commencing PD ‐1 checkpoint inhibitor therapy in five of 15 melanoma patients, including both the patients who developed sarcoidosis during the course of therapy. Conclusion Our findings support prior literature implicating Th17.1 cells in the pathogenesis of sarcoidosis. However, we demonstrate these findings in patients with melanoma prior to administration of checkpoint therapy and before the onset of clinically symptomatic sarcoidosis. The identification of elevated Th17.1 cells in melanoma patients who have not developed sarcoidosis may reflect the established association between melanoma and sarcoidosis. With some patients receiving these agents over a prolonged period, the clinical course of immunotherapy‐induced sarcoidosis is uncertain.