Recurrent SERPINB3 and SERPINB4 mutations in patients who respond to anti-CTLA4 immunotherapy.
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.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.|Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.|Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Nadeem
N
Riaz
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Jonathan J
0000-0003-0951-510X
JJ
Havel
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Sviatoslav M
SM
Kendall
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Vladimir
V
Makarov
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Logan A
LA
Walsh
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Alexis
0000-0002-1335-7813
A
Desrichard
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Nils
N
Weinhold
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.|Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.|Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Timothy A
TA
Chan
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000235:genetics*; D015331:Cohort Studies; D006801:Humans; D000074324:Ipilimumab; D008545:Melanoma / Q000235:genetics* / Q000628:therapy*; D009154:Mutation; D015843:Serpins / Q000235:genetics*; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000074324:Ipilimumab; D015843:Serpins; C051072:squamous cell carcinoma-related antigen
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