Department of Radiology, Stanford University School of Medicine, Stanford, California.
Molecular Imaging Research Center of Harbin Medical University, Harbin, Heilongjiang, China.
Cancer Res. 2020 Jul 15;80(14):3023-3032. doi: 10.1158/0008-5472.CAN-19-3265. Epub 2020 Mar 10.
Immunotherapy is innovating clinical cancer management. Nevertheless, only a small fraction of patient's benefit from current immunotherapies. To improve clinical management of cancer immunotherapy, it is critical to develop strategies for response monitoring and prediction. In this study, we describe inducible T-cell costimulator (ICOS) as a conserved mediator of immune response across multiple therapy strategies. ICOS expression was evaluated by flow cytometry, Zr-DFO-ICOS mAb PET/CT imaging was performed on Lewis lung cancer models treated with different immunotherapy strategies, and the change in tumor volume was used as a read-out for therapeutic response. ImmunoPET imaging of ICOS enabled sensitive and specific detection of activated T cells and early benchmarking of immune response. A STING (stimulator of interferon genes) agonist was identified as a promising therapeutic approach in this manner. The STING agonist generated significantly stronger immune responses as measured by ICOS ImmunoPET and delayed tumor growth compared with programmed death-1 checkpoint blockade. More importantly, ICOS ImmunoPET enabled early and robust prediction of therapeutic response across multiple treatment regimens. These data show that ICOS is an indicator of T-cell-mediated immune response and suggests ICOS ImmunoPET as a promising strategy for monitoring, comparing, and predicting immunotherapy success in cancer. SIGNIFICANCE: ICOS ImmunoPET is a promising strategy to noninvasively predict and monitor immunotherapy response..
免疫疗法正在创新癌症临床管理。然而，目前的免疫疗法只有一小部分患者受益。为了改善癌症免疫疗法的临床管理，开发用于反应监测和预测的策略至关重要。在这项研究中，我们描述了诱导性 T 细胞共刺激因子（ICOS）作为多种治疗策略中免疫反应的保守介质。通过流式细胞术评估 ICOS 表达，对接受不同免疫治疗策略治疗的 Lewis 肺癌模型进行 Zr-DFO-ICOS mAb PET/CT 成像，并用肿瘤体积变化作为治疗反应的读出。ICOS 的免疫 PET 成像能够灵敏和特异地检测激活的 T 细胞，并早期基准免疫反应。以这种方式鉴定出 STING（干扰素基因刺激物）激动剂是一种很有前途的治疗方法。与程序性死亡-1 检查点阻断相比，STING 激动剂产生的免疫反应要强得多，这可以通过 ICOS 免疫 PET 进行测量，并延迟肿瘤生长。更重要的是，ICOS 免疫 PET 能够在多种治疗方案中进行早期和强大的治疗反应预测。这些数据表明 ICOS 是 T 细胞介导的免疫反应的指标，并表明 ICOS 免疫 PET 是监测、比较和预测癌症免疫治疗成功的有前途的策略。意义：ICOS 免疫 PET 是一种有前途的非侵入性预测和监测免疫治疗反应的策略。
