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

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1097/cji.0000000000000425

Publication Info

Oswalt, Cameron J, Rami N Al-Rohil, Bala Theivanthiran, Tarek Haykal, April KS Salama, Nicholas C DeVito, Alisha Holtzhausen, Dennis C Ko, et al. (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.

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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

Salama

April Kelly Scott Salama

Associate Professor of Medicine
DeVito

Nicholas Christian DeVito

Assistant Professor of Medicine

I am an Assistant Professor of Medical Oncology who primarily treats patients with colon cancer and gastroesophageal cancers. My laboratory and translational research is focused on tumor immune evasion and immunotherapy, particularly in the setting of metastasis. This work has led to a specific interest in tumor-mediated development of dendritic cell tolerance and suppressive myeloid populations. The ultimate goal of this research is to create biomarker-directed immunotherapies for advanced gastrointestinal cancers.

Ko

Dennis Ko

Associate Professor in Molecular Genetics and Microbiology

Using Pathogens to Decipher Genetic Variation Connecting Cell Biology and Disease Susceptibility
Despite 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 genetic basis for differences in susceptibility to infection and related inflammatory disorders. We approach this question through a combination of experimental and computational approaches that combine high-throughput cell biology with quantitative human genetics. The identified genetic differences serve as the starting point for exploring new cell biology and human disease susceptibility genes.


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