免疫基因表达特征正在成为免疫治疗 (IO) 的潜在生物标志物。 VIGex 是一种 12 基因表达分类器，在 nCounter (Nanostring) 和 RNA 测序 (RNA-seq) 测定中开发，并在实验室中进行了分析验证。 VIGex 将肿瘤样本分为热亚组、中冷亚组 (I-Cold) 和冷亚组。 VIGex-Hot 与更好的 IO 治疗结果相关。在这里，我们研究了 INSPIRE II 期临床试验（ClinicalTrials.gov 标识符：NCT02644369）中接受派姆单抗治疗的患者的独立数据集中 VIGex 和其他 IO 生物标志物的表现。晚期实体瘤患者接受了派姆单抗 200 mg IV 治疗每 3 周一次。来自基线肿瘤样本的肿瘤 RNA-seq 数据通过 VIGex 算法进行分类。使用定制的 Signatera 检测在基线和第 3 周期开始时测量循环肿瘤 DNA (ctDNA)。将 VIGex-Hot 与 VIGex I-Cold Cold 进行比较，并根据 VIGex 亚组的组合和第 3 个周期 ctDNA 相对于基线的变化 (ΔctDNA) 来定义 4 组。 入组 76 名患者，包括 16 名卵巢、 12 种乳腺癌、12 种头颈癌、10 种黑色素瘤和 26 种其他肿瘤类型。 VIGex-Hot 的客观缓解率为 24%，I-Cold/Cold 的客观缓解率为 10%。当纳入根据肿瘤类型、肿瘤突变负荷和 PD-L1 免疫组织化学调整的多变量模型时，VIGex-Hot 亚组与较高的总生存期 (OS) 和无进展生存期 (PFS) 相关。添加 ΔctDNA 提高了基线 VIGex 分类对 OS 和 PFS 的预测性能。我们的数据表明，在基线 VIGex 中添加 ΔctDNA 可以改进 IO 的预测。

Immune gene expression signatures are emerging as potential biomarkers for immunotherapy (IO). VIGex is a 12-gene expression classifier developed in both nCounter (Nanostring) and RNA sequencing (RNA-seq) assays and analytically validated across laboratories. VIGex classifies tumor samples into hot, intermediate-cold (I-Cold), and cold subgroups. VIGex-Hot has been associated with better IO treatment outcomes. Here, we investigated the performance of VIGex and other IO biomarkers in an independent data set of patients treated with pembrolizumab in the INSPIRE phase II clinical trial (ClinicalTrials.gov identifier: NCT02644369).Patients with advanced solid tumors were treated with pembrolizumab 200 mg IV once every 3 weeks. Tumor RNA-seq data from baseline tumor samples were classified by the VIGex algorithm. Circulating tumor DNA (ctDNA) was measured at baseline and start of cycle 3 using the bespoke Signatera assay. VIGex-Hot was compared with VIGex I-Cold + Cold and four groups were defined on the basis of the combination of VIGex subgroups and the change in ctDNA at cycle 3 from baseline (ΔctDNA).Seventy-six patients were enrolled, including 16 ovarian, 12 breast, 12 head and neck cancers, 10 melanoma, and 26 other tumor types. Objective response rate was 24% in VIGex-Hot and 10% in I-Cold/Cold. VIGex-Hot subgroup was associated with higher overall survival (OS) and progression-free survival (PFS) when included in a multivariable model adjusted for tumor type, tumor mutation burden, and PD-L1 immunohistochemistry. The addition of ΔctDNA improved the predictive performance of the baseline VIGex classification for both OS and PFS.Our data indicate that the addition of ΔctDNA to baseline VIGex may refine prediction for IO.