Although more than a decade has passed since the approval of immune checkpoint inhibitors (ICIs) for the treatment of melanoma and non-small-cell lung, breast and gastrointestinal cancers, many patients still show limited response. US Food and Drug Administration (FDA)-approved biomarkers include programmed cell death 1 ligand 1 (PDL1) expression, microsatellite status (that is, microsatellite instability-high (MSI-H)) and tumour mutational burden (TMB), but these have limited utility and/or lack standardized testing approaches for pan-cancer applications. Tissue-based analytes (such as tumour gene signatures, tumour antigen presentation or tumour microenvironment profiles) show a correlation with immune response, but equally, these demonstrate limited efficacy, as they represent a single time point and a single spatial assessment. Patient heterogeneity as well as inter- and intra-tumoural differences across different tissue sites and time points represent substantial challenges for static biomarkers. However, dynamic biomarkers such as longitudinal biopsies or novel, less-invasive markers such as blood-based biomarkers, radiomics and the gut microbiome show increasing potential for the dynamic identification of ICI response, and patient-tailored predictors identified through neoadjuvant trials or novel ex vivo tumour models can help to personalize treatment. In this Perspective, we critically assess the multiple new static, dynamic and patient-specific biomarkers, highlight the newest consortia and trial efforts, and provide recommendations for future clinical trials to make meaningful steps forwards in the field.

尽管免疫检查点抑制剂 （ICI） 被批准用于治疗黑色素瘤和非小细胞肺癌、乳腺癌和胃肠道癌已经过去了十多年，但许多患者的反应仍然有限。美国食品药品监督管理局 （FDA） 批准的生物标志物包括程序性细胞死亡 1 配体 1 （PDL1） 表达、微卫星状态（即微卫星不稳定性高 （MSI-H））和肿瘤突变负荷 （TMB），但这些用途有限和/或缺乏泛癌应用的标准化检测方法。基于组织的分析物（如肿瘤基因特征、肿瘤抗原呈递或肿瘤微环境谱）显示与免疫反应相关，但同样，这些分析物的疗效有限，因为它们代表单个时间点和单个空间评估。患者的异质性以及不同组织部位和时间点的肿瘤间和肿瘤内差异对静态生物标志物构成了巨大的挑战。然而，动态生物标志物（如纵向活检）或新的、侵入性较小的标志物（如基于血液的生物标志物、放射组学和肠道微生物组）显示出动态识别 ICI 反应的潜力越来越大，通过新辅助试验或新型离体肿瘤模型确定的患者定制预测因子有助于个性化治疗。在这个观点中，我们批判性地评估了多种新的静态、动态和患者特异性生物标志物，突出了最新的联盟和试验工作，并为未来的临床试验提供建议，以便在该领域取得有意义的进展。