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Identification of a Germline Pyrin Variant in a Metastatic Melanoma Patient With Multiple Spontaneous Regressions and Immune-related Adverse Events.

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Date
2022-07
Authors
Oswalt, Cameron J
Al-Rohil, Rami N
Theivanthiran, Bala
Haykal, Tarek
Salama, April KS
DeVito, Nicholas C
Holtzhausen, Alisha
Ko, Dennis C
Hanks, Brent A
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Abstract
The mechanisms underlying tumor immunosurveillance and their association with the immune-related adverse events (irAEs) associated with checkpoint inhibitor immunotherapies remain poorly understood. We describe a metastatic melanoma patient exhibiting multiple episodes of spontaneous disease regression followed by the development of several irAEs during the course of anti-programmed cell death protein 1 antibody immunotherapy. Whole-exome next-generation sequencing studies revealed this patient to harbor a pyrin inflammasome variant previously described to be associated with an atypical presentation of familial Mediterranean fever. This work highlights a potential role for inflammasomes in the regulation of tumor immunosurveillance and the pathogenesis of irAEs.
Type
Journal article
Subject
Humans
Melanoma
Neoplasms, Second Primary
Immunotherapy
Pyrin
Antineoplastic Agents, Immunological
Permalink
https://hdl.handle.net/10161/26401
Published Version (Please cite this version)
10.1097/cji.0000000000000425
Publication Info
Oswalt, Cameron J; Al-Rohil, Rami N; Theivanthiran, Bala; Haykal, Tarek; Salama, April KS; DeVito, Nicholas C; ... Hanks, Brent A (2022). Identification of a Germline Pyrin Variant in a Metastatic Melanoma Patient With Multiple Spontaneous Regressions and Immune-related Adverse Events. Journal of immunotherapy (Hagerstown, Md. : 1997), 45(6). pp. 284-290. 10.1097/cji.0000000000000425. Retrieved from https://hdl.handle.net/10161/26401.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Al-Rohil

Rami Nayef Al-Rohil

Associate Professor of Pathology
I am dermatopathologist with special interest in melanocytic pathology (including molecular alterations and tests that aid in predicting their biologic behavior), and soft tissue pathology
DeVito

Nicholas Christian DeVito

Medical Instructor in the Department of Medicine
I am an instructor of Medical Oncology who primarily treats patients with gastrointestinal malignancies. My laboratory and translational research is focused on tumor immune evasion and immunotherapy, with a specific interest in dendritic cell tolerance.
Hanks

Brent A. Hanks

Associate Professor of Medicine
We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers
Ko

Dennis Ko

Associate Professor in Molecular Genetics and Microbiology
Using Pathogens to Decipher Genetic Variation Connecting Cell Biology and Disease SusceptibilityDespite improvements in public health, advancements in vaccines, and the development of many classes of antibiotics, infectious disease is still responsible for over a quarter of all deaths worldwide. However, even for the most devastating of pandemics, individuals demonstrate a large variability in the severity of infection. The long-term goal of the lab is to understand the ge
Salama

April Kelly Scott Salama

Associate Professor of Medicine
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