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

J Immunother. 2022 Jul-Aug;45(6):284-290. doi: 10.1097/CJI.0000000000000425. Epub 2022 May 30.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents, Immunological* / therapeutic use
  • Humans
  • Immunotherapy / adverse effects
  • Melanoma* / diagnosis
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Neoplasms, Second Primary* / etiology
  • Pyrin


  • Antineoplastic Agents, Immunological
  • Pyrin