@article{3078375, title = "A Th1/IFNG gene signature is prognostic in the adjuvant setting of resectable high-risk melanoma but not in non-small cell lung cancer", author = "Dizier, B. and Callegaro, A. and Debois, M. and Dreno, B. and Hersey, P. and Gogas, H.J. and Kirkwood, J.M. and Vansteenkiste, J.F. and Sequist, L.V. and Atanackovic, D. and Goeman, J. and van Houwelingen, H. and Salceda, S. and Wang, F. and Therasse, P. and Debruyne, C. and Spiessens, B. and Brichard, V.G. and Louahed, J. and Ulloa-Montoya, F.", journal = "Clinical Cancer Research", year = "2020", volume = "26", number = "7", pages = "1725-1735", publisher = "American Association for Cancer Research Inc.", issn = "1078-0432", doi = "10.1158/1078-0432.CCR-18-3717", keywords = "gamma interferon; tumor marker, adult; Article; cancer prognosis; cancer surgery; controlled study; disease free survival; high risk patient; human; lymph node metastasis; major clinical study; melanoma; non small cell lung cancer; overall survival; priority journal; prospective study; protein expression level; Th1 cell; tumor associated leukocyte", abstract = "Purpose: Immune components of the tumor microenvironment (TME) have been associated with disease outcome. We prospectively evaluated the association of an immune-related gene signature (GS) with clinical outcome in melanoma and non-small cell lung cancer (NSCLC) tumor samples from two phase III studies. Experimental Design: The GS was prospectively validated using an adaptive signature design to optimize it for the sample type and technology used in phase III studies. One-third of the samples were used as “training set”; the remaining two thirds, constituting the “test set,” were used for the prospective validation of the GS. Results: In the melanoma training set, the expression level of eight Th1/IFNg-related genes in tumor-positive lymph node tissue predicted the duration of disease-free survival (DFS) and overall survival (OS) in the placebo arm. This GS was prospectively and independently validated as prognostic in the test set. Building a multivariate Cox model in the test set placebo patients from clinical covariates and the GS score, an increased number of melanoma-involved lymph nodes and the GS were associated with DFS and OS. This GS was not associated with DFS in NSCLC, although expression of the Th1/IFNg -related genes was associated with the presence of lymphocytes in tumor samples in both indications. Conclusions: These findings provide evidence that expression of Th1/IFNg genes in the TME, as measured by this GS, is associated with clinical outcome in melanoma. This suggests that, using this GS, patients with stage IIIB/C melanoma can be classified into different risk groups. © 2019 American Association for Cancer Research." }