title: IFNγ Mutations Prompt CTLA-4 Inhibitor Resistance.
abstract: A recent study pinpoints loss of IFNγ signaling as one reason why many patients do not respond to the CTLA-4 inhibitor ipilimumab. Analyzing whole-exome tumor sequencing data from 16 patients with melanoma, the researchers found multiple copy-number alterations that led to the loss of key IFNγ pathway genes in 12 ipilimumab nonresponders. Mice bearing melanoma tumors that lacked one of these genes, IFNGR1, also had an impaired response to anti-CTLA-4 therapy and significantly reduced overall survival, compared with their counterparts whose tumors had intact IFNGR1.
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics*; D051379:Mice; D009154:Mutation; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; C573415:IFNG protein, human; D000074324:Ipilimumab; D007371:Interferon-gamma