Rapisuwon, SutheeIzar, BenjaminBatenchuk, CoryAvila, AlexandreMei, ShaolinSorger, PeterParks, Jerry MCooper, Sarah JWagner, DavidZeck, Jay CCharabaty, Aline JAtkins, Michael B2019-03-112019-03-112019-03-04Journal for ImmunoTherapy of Cancer. 2019 Mar 04;7(1):61https://doi.org/10.1186/s40425-019-0533-0https://doi.org/10.20381/ruor-23140http://hdl.handle.net/10393/38888Abstract Balancing the potential for durable remissions with autoimmune-like toxicities is a key clinical challenge in the use of immune checkpoint inhibitors (ICI). Certain toxicities are associated with an increased response rate; however, the molecular underpinnings of this association are poorly understood. Here, we report a patient with wide spread uveal melanoma who had an exceptional response to treatment with ipilimumab and nivolumab, but suffered severe immune-related sequelae, including central serous retinopathy with retinal detachment, tinnitus, and vitiligo resembling Vogt-Koyanagi-Harada disease, and refractory enteritis. TCR-sequencing of the primary tumor, a hepatic metastasis, duodenal biopsy and peripheral blood mononuclear cells, identified the identical T cell clone in all four tissues. This case provides preliminary evidence for cross-reactivity as a mechanism for the association between effect and toxicity of ICIs.Journal Article2019-03-11enThe Author(s).