Lauwerys Louis, Smits Evelien, Van den Wyngaert Tim, Elvas Filipe
Molecular Imaging Center Antwerp (MICA), Integrated Personalized and Precision Oncology Network (IPPON), Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
Biomedicines. 2022 May 5;10(5):1074. doi: 10.3390/biomedicines10051074.
Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body's immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8 T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided.
癌症免疫疗法是一种不断发展且前景广阔的癌症治疗方法，它利用人体免疫系统来有效消除肿瘤。重要的是，免疫疗法已经改变了许多癌症的治疗格局，带来了显著的肿瘤反应并提高了患者生存率。然而，尽管肿瘤治疗效果显著且患者生存期延长，但只有一小部分患者有反应，其他患者可能会出现与这些疗法相关的免疫相关不良事件，这会带来相当高的成本。因此，仍迫切需要提高从这些治疗中获益的患者比例和/或增强免疫介导的肿瘤反应持久性的策略。目前，由于肿瘤内在的异质性以及组织活检具有侵入性，血液或组织生物标志物的检测已显示出采样局限性。此外，传统成像方式无法充分捕捉这些疗法独特的反应模式。因此，正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）等使用特定放射性示踪剂的非侵入性、灵敏且定量的分子成像技术，已越来越多地用于免疫反应的纵向全身监测。免疫疗法依赖于肿瘤病灶处CD8 T细胞和自然杀伤细胞（NK）的效应功能；因此，监测这些细胞毒性免疫细胞对于评估治疗反应具有重要价值。不同的免疫细胞靶点已被研究作为免疫疗法反应的替代标志物，这推动了多种成像剂的开发。在本综述中，总结了正在研究的用于监测免疫效应细胞功能状态的靶点和放射性示踪剂，并回顾了它们在免疫相关反应成像中的应用及其局限性和陷阱，其中多种已转化应用于临床。最后，还介绍了新兴的效应免疫细胞成像策略和未来发展方向。
