Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical responses to immunotherapy. In this study, we used next-generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed to identify biomarkers associated with immunotherapy response and assess the potential application of simple non-invasive blood biomarkers as a therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICIs. Interestingly, in both, a common lymphocytic activation signature can be identified associated with the efficient response to immunotherapy, including a blood-specific CD8+ T cell activation/proliferation signature which predicts the immunotherapy response.
血液生物标志物是开发非侵入性免疫肿瘤学检测方法的理想候选物。然而迄今为止,尚无血液生物标志物被验证可用于预测免疫治疗的临床反应。本研究在临床前MIBC小鼠模型中,对从全血和肿瘤样本提取的总RNA进行新一代测序(RNAseq)。我们旨在识别与免疫治疗反应相关的生物标志物,并评估相较于组织生物标志物,简单的非侵入性血液生物标志物作为治疗决策检测手段的潜在应用价值。研究发现,循环免疫细胞与肿瘤微环境对免疫检查点抑制剂表现出高度器官特异性的转录反应。值得注意的是,在这两种体系中均可识别出与免疫治疗有效反应相关的共同淋巴细胞活化特征,其中包括能够预测免疫治疗反应的特异性血液CD8+ T细胞活化/增殖特征。