A T-helper 1/interferon- gene signature is prognostic in the adjuvant setting of resectable high-risk melanoma but not in non-small cell lung cancer.

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. METHODS: 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 T-helper (Th1)/interferon (IFN)-γ-related genes in tumor-positive lymph node (LN) 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 LNs and the GS were associated with DFS and OS. This GS was not associated with DFS in NSCLC, although expression of the Th1/IFN-γ-related genes was associated with the presence of lymphocytes in tumor samples in both indications. CONCLUSION: These findings provide evidence that expression of Th1/IFN-γ 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.