Anna J Lomax1, Helen M McGuire2,3, Catriona McNeil1,2,4, Clara J Choi2,3, Peter Hersey3,5, Deme Karikios1,6, Kerwin Shannon1,2,4,5, Sebastian van Hal2,4, Urszula Carr7, Anne Crotty8, Sandeep K Gupta9,10, Jane Hollingsworth2,4, Haewon Kim2,4, Barbara Fazekas de St Groth2,3, Neil McGill2,4. 1. Chris O'Brien Lifehouse, Sydney, New South Wales, Australia. 2. University of Sydney, Sydney, New South Wales, Australia. 3. Centenary Institute, Sydney, New South Wales, Australia. 4. Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. 5. Melanoma Institute Australia, Sydney, New South Wales, Australia. 6. Nepean Hospital, Sydney, New South Wales, Australia. 7. Kossard Dermatopathologists, Sydney, New South Wales, Australia. 8. Pathology North - Hunter, Newcastle, New South Wales, Australia. 9. John Hunter and Calvary Mater Hospitals, Newcastle, New South Wales, Australia. 10. University of Newcastle, Newcastle, New South Wales, Australia.
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.
AIM: Sarcoidosis is a multisystem granulomatous disease. This condition has a documented association with the diagnosis of melanoma and can be induced in melanomapatients receiving anti-neoplastic therapy. We evaluated a case series of melanomapatients 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 melanomapatients 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 melanomapatients, 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 melanomapatients 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.
Authors: Subashini Sharon Gnanendran; Lauren Maree Turner; James Austin Miller; Shelley Ji Eun Hwang; Andrew Charles Miller Journal: Curr Treat Options Oncol Date: 2020-03-19
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