抗PD1/PDL1免疫检查点抑制剂（ICI）改变了晚期非小细胞肺癌（NSCLC）患者的预后。然而，其响应率仍然令人失望，毒性可能危及生命，因此迫切需要找到预测疗效的生物标志物。免疫排斥恒常性标记（ICR）是一种由20个基因表达标记组成的细胞毒性免疫反应标记，在某些实体肿瘤中具有预后价值。我们的目标是评估ICR对于从抗PD1/PDL1获益的NSCLC晚期患者的预测价值。我们对44个来自接受ICI单药治疗的NSCLC患者原发肿瘤进行了回顾性分析，其中至少在第二线转移治疗中使用。采用nCounter®分析系统和PanCancer免疫分析面板进行了转录组分析。然后，我们将我们的数据与来自四个公共基因表达数据集的临床生物学数据进行了混合，共计162例接受单药抗PD1/PDL1治疗的NSCLC患者。对所有样本应用了ICR，寻找ICR类别与持久性临床效益（DCB）之间的相关性，DCB定义为根据RECIST 1.1，在ICI开始后至少6个月的稳定疾病或客观反应。DCB率为29％；22％的样本被归类为ICR1，30％为ICR2，22％为ICR3，26％为ICR4。这些类别与临床病理变量无关，但显示出ICR1到ICR4在免疫应答量化/定性标记中的富集。与ICR1类相比，ICR2-4类与DCB率相比较高，达到5.65倍。在多变量分析中，ICR分类与DCB相关，独立于PDL1表达和其他预测的免疫标志物。相比之下，在未接受ICI治疗的556例NSCLC TCGA患者中，ICR分类与无病生存期无关。这20个基因的ICR标记与受益于抗PD1/PDL1 ICI的晚期NSCLC患者独立相关。需要在更大的回顾性和前瞻性系列中进行验证。© 2023. BioMed Central Ltd., part of Springer Nature.

Anti-PD1/PDL1 immune checkpoint inhibitors (ICI) transformed the prognosis of patients with advanced non-small cell lung cancer (NSCLC). However, the response rate remains disappointing and toxicity may be life-threatening, making urgent identification of biomarkers predictive for efficacy. Immunologic Constant of Rejection signature (ICR) is a 20-gene expression signature of cytotoxic immune response with prognostic value in some solid cancers. Our objective was to assess its predictive value for benefit from anti-PD1/PDL1 in patients with advanced NSCLC.We retrospectively profiled 44 primary tumors derived from NSCLC patients treated with ICI as single-agent in at least the second-line metastatic setting. Transcriptomic analysis was performed using the nCounter® analysis system and the PanCancer Immune Profiling Panel. We then pooled our data with clinico-biological data from four public gene expression data sets, leading to a total of 162 NSCLC patients treated with single-agent anti-PD1/PDL1. ICR was applied to all samples and correlation was searched between ICR classes and the Durable Clinical Benefit (DCB), defined as stable disease or objective response according to RECIST 1.1 for a minimum of 6 months after the start of ICI.The DCB rate was 29%; 22% of samples were classified as ICR1, 30% ICR2, 22% ICR3, and 26% ICR4. These classes were not associated with the clinico-pathological variables, but showed enrichment from ICR1 to ICR4 in quantitative/qualitative markers of immune response. ICR2-4 class was associated with a 5.65-fold DCB rate when compared with ICR1 class. In multivariate analysis, ICR classification remained associated with DCB, independently from PDL1 expression and other predictive immune signatures. By contrast, it was not associated with disease-free survival in 556 NSCLC TCGA patients untreated with ICI.The 20-gene ICR signature was independently associated with benefit from anti-PD1/PDL1 ICI in patients with advanced NSCLC. Validation in larger retrospective and prospective series is warranted.© 2023. BioMed Central Ltd., part of Springer Nature.