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Int J Rheum Dis ; 20(9): 1277-1285, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28480561

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 (CCR6+ CCR4- CXCR3+ CCR10- ) 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.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Immunophenotyping , Immunotherapy/adverse effects , Melanoma/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Sarcoidosis, Pulmonary/chemically induced , Skin Neoplasms/drug therapy , Th17 Cells/drug effects , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Biomarkers/blood , Biopsy , Female , Humans , Male , Melanoma/blood , Melanoma/immunology , Melanoma/secondary , Middle Aged , Neoplasm Staging , Phenotype , Positron-Emission Tomography , Predictive Value of Tests , Programmed Cell Death 1 Receptor/immunology , Sarcoidosis, Pulmonary/blood , Sarcoidosis, Pulmonary/diagnosis , Sarcoidosis, Pulmonary/drug therapy , Skin Neoplasms/blood , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Th17 Cells/immunology , Th17 Cells/metabolism , Tomography, X-Ray Computed , Treatment Outcome
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