A Th1/IFN gamma gene signature is prognostic in the adjuvant setting of resectable high-risk melanoma but not in non-small cell lung cancer

Dizier, B.; Callegaro, A.; Debois, M.; Dreno, B.; Hersey, P.; Gogas, H.J.; Kirkwood, J.M.; Vansteenkiste, J.F.; Sequist, L.V.; Atanackovic, D.; Goeman, J.; Houwelingen, H. van; Salceda, S.; Wang, F.; Therasse, P.; Debruyne, C.; Spiessens, B.; Brichard, V.G.; Louahed, J.; Ulloa-Montoya, F.

doi:doi:10.1158/1078-0432.CCR-18-3717

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/IFN gamma-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...Show morePurpose: 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/IFN gamma-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/IFN gamma-related genes was associated with the presence of lymphocytes in tumor samples in both indications.Conclusions: These findings provide evidence that expression of Th1/IFN gamma 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.Show less

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A Th1/IFN gamma gene signature is prognostic in the adjuvant setting of resectable high-risk melanoma but not in non-small cell lung cancer