Hegi-Johnson Fiona, Rudd Stacey, Hicks Rodney J, De Ruysscher Dirk, Trapani Joseph A, John Thomas, Donnelly Paul, Blyth Benjamin, Hanna Gerard, Everitt Sarah, Roselt Peter, MacManus Michael P
Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
NPJ Precis Oncol. 2022 Apr 7;6(1):24. doi: 10.1038/s41698-022-00263-x.
Immune checkpoint inhibitors and related molecules can achieve tumour regression, and even prolonged survival, for a subset of cancer patients with an otherwise dire prognosis. However, it remains unclear why some patients respond to immunotherapy and others do not. PET imaging has the potential to characterise the spatial and temporal heterogeneity of both immunotherapy target molecules and the tumor immune microenvironment, suggesting a tantalising vision of personally-adapted immunomodulatory treatment regimens. Personalised combinations of immunotherapy with local therapies and other systemic therapies, would be informed by immune imaging and subsequently modified in accordance with therapeutically induced immune environmental changes. An ideal PET imaging biomarker would facilitate the choice of initial therapy and would permit sequential imaging in time-frames that could provide actionable information to guide subsequent therapy. Such imaging should provide either prognostic or predictive measures of responsiveness relevant to key immunotherapy types but, most importantly, guide key decisions on initiation, continuation, change or cessation of treatment to reduce the cost and morbidity of treatment while enhancing survival outcomes. We survey the current literature, focusing on clinically relevant immune checkpoint immunotherapies, for which novel PET tracers are being developed, and discuss what steps are needed to make this vision a reality.
免疫检查点抑制剂及相关分子能够使一部分原本预后极差的癌症患者实现肿瘤消退,甚至延长生存期。然而,仍不清楚为何有些患者对免疫疗法有反应而其他患者则没有。正电子发射断层扫描(PET)成像有潜力描绘免疫疗法靶分子和肿瘤免疫微环境的空间及时间异质性,这为个性化免疫调节治疗方案勾勒出了诱人的前景。免疫成像可为免疫疗法与局部治疗及其他全身治疗的个性化联合提供依据,并随后根据治疗引起的免疫环境变化进行调整。理想的PET成像生物标志物将有助于初始治疗的选择,并能在可提供可指导后续治疗的可操作信息的时间范围内进行序贯成像。这种成像应提供与关键免疫疗法类型相关的反应性的预后或预测指标,但最重要的是,指导关于治疗开始、继续、改变或停止的关键决策,以降低治疗成本和发病率,同时提高生存结果。我们综述了当前的文献,重点关注正在开发新型PET示踪剂的临床相关免疫检查点免疫疗法,并讨论了要实现这一愿景需要采取哪些步骤。