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Exceptional response and multisystem autoimmune-like toxicities associated with the same T cell clone in a patient with uveal melanoma treated with immune checkpoint inhibitors
oleh: Suthee Rapisuwon, Benjamin Izar, Cory Batenchuk, Alexandre Avila, Shaolin Mei, Peter Sorger, Jerry M. Parks, Sarah J. Cooper, David Wagner, Jay C. Zeck, Aline J. Charabaty, Michael B. Atkins
Format: | Article |
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Diterbitkan: | BMJ Publishing Group 2019-03-01 |
Deskripsi
Abstract 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.