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/IFNγ-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/IFNγ-related genes was associated with the presence of lymphocytes in tumor samples in both indications. CONCLUSIONS These findings provide evidence that expression of Th1/IFNγ 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.

中文翻译：

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Th1 /IFNγ基因签名在可切除的高危黑色素瘤的辅助治疗中预后，但在非小细胞肺癌中没有。

目的肿瘤微环境（TME）的免疫成分已与疾病预后相关。我们前瞻性地评估了来自两项III期研究的黑色素瘤和非小细胞肺癌（NSCLC）肿瘤样本中免疫相关基因标记（GS）与临床结局的关联。实验设计使用自适应签名设计对GS进行前瞻性验证，以针对III期研究中使用的样品类型和技术对其进行优化。三分之一的样本用作“训练集”；剩下的三分之二（构成“测试集”）用于GS的前瞻性验证。结果在黑色素瘤训练集中，肿瘤阳性淋巴结组织中八个Th1 /IFNγ相关基因的表达水平预测了安慰剂组的无病生存期（DFS）和总体生存期（OS）。该GS已在测试集中进行了前瞻性和独立的预后验证。根据临床协变量和GS评分在测试组安慰剂患者中建立多元Cox模型，黑色素瘤累及的淋巴结和GS的增加与DFS和OS相关。尽管在两种适应症中，Th1 /IFNγ相关基因的表达与肿瘤样品中淋巴细胞的存在有关，但该GS与NSCLC中的DFS无关。结论这些发现提供了证据，证明通过该GS检测的TME中Th1 /IFNγ基因的表达与黑色素瘤的临床结局有关。这表明，