Loss of IFN-g signaling in tumor cells associates with primary resistance to anti-CTLA-4 therapy

"Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-?, which is a critical cytokine for host immune responses. However, the role of IFN-? signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here we demonstrate that, based upon exome sequencing data, patients identified as non-responders to anti-CTLA-4 (ipilimumab) harbor a much higher genomic defects in the IFN-? pathway genes than melanoma patients who had clinical response to ipilimumab therapy."