Recurrent SERPINB3 and SERPINB4 mutations in patients who respond to anti-CTLA4 immunotherapy

Nat Genet. 2016 Nov;48(11):1327-1329. doi: 10.1038/ng.3677. Epub 2016 Sep 26.


Immune checkpoint blockade has shown significant promise as an anticancer treatment, yet the determinants of response are not completely understood. Here we show that somatic mutations in SERPINB3 and SERPINB4 are associated with survival after anti-CTLA4 immunotherapy in two independent cohorts of patients with melanoma (n = 174). Interestingly, serpins are homologs of the well-known ovalbumin antigen and are associated with autoimmunity. Our findings have implications for the personalization of immunotherapy.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Neoplasm / genetics*
  • Cohort Studies
  • Humans
  • Ipilimumab
  • Melanoma / genetics*
  • Melanoma / therapy*
  • Mutation*
  • Serpins / genetics*
  • Survival Analysis


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Ipilimumab
  • Serpins
  • squamous cell carcinoma-related antigen