Karachaliou, NikiGonzalez-Cao, MariaCrespo, GuillermoDrozdowskyj, AnaAldeguer, ErikaGimenez-Capitan, AnaTeixido, CristinaAngel Molina-Vila, MiguelViteri, SantiagoDe los Llanos Gil, MariaMartin Algarra, SalvadorPerez-Ruiz, ElisabethMarquez-Rodas, IvanRodriguez-Abreu, DelvysBlanco, RemediosPuertolas, TeresaAngeles Royo, MariaRosell, Rafael2025-01-072025-01-072018-01-181758-8340https://hdl.handle.net/10668/26708Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-gamma). We have explored whether the expression of IFNG, the gene encoding IFN-gamma, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined.Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR. STAT3 and Rantes, YAP1 and CXCL5, DNMT1, RIG1 and TET1, EOMES, IFNG, PD-L1 and CTLA4, IKBKE and NFATC1 mRNA were examined. PD-L1 protein expression in tumor and immune cells and stromal infiltration of CD8(+) T-cells were also evaluated. Progression-free survival and overall survival were estimated.Results: A total of 17 NSCLC patients received nivolumab and 21 melanoma patients received pembrolizumab. Progression-free survival with nivolumab was significantly longer in NSCLC patients with high versus low IFNG expression (5.1 months versus 2 months, p = 0.0124). Progression-free survival with pembrolizumab was significantly longer in melanoma patients with high versus low IFNG expression (5.0 months versus 1.9 months, p = 0.0099). Significantly longer overall survival was observed for melanoma patients with high versus low IFNG expression (not reached versus 10.2 months p = 0.0183). There was a trend for longer overall survival for NSCLC patients with high versus low IFNG expression.Conclusions: IFN-gamma is an important marker for prediction of response to immune checkpoint blockade. Further research is warranted in order to validate whether IFNG is more accurate than PD-L1.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/Immunotherapyinterferon-gammaPD-1PD-L1lung cancermelanomaPd-1 blockadeOpen-labelIfn-gammaT-cellsClinical-responseCtla-4 blockadeViral mimicryDouble-blindExpressionChemotherapyresearch article29383037open access10.1177/17588340177497481758-8359https://journals.sagepub.com/doi/pdf/10.1177/1758834017749748429010000001