Marciscano Ariel E, Thorek Daniel L J
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Adv Radiat Oncol. 2018 Oct 23;3(4):534-547. doi: 10.1016/j.adro.2018.07.006. eCollection 2018 Oct-Dec.
The intersection of immunotherapy and radiation oncology is a rapidly evolving area of preclinical and clinical investigation. The strategy of combining radiation and immunotherapy to enhance local and systemic antitumor immune responses is intriguing yet largely unproven in the clinical setting because the mechanisms of synergy and the determinants of therapeutic response remain undefined. In recent years, several noninvasive molecular imaging approaches have emerged as a platform to interrogate the tumor immune microenvironment. These tools have the potential to serve as robust biomarkers for cancer immunotherapy and may hold several advantages over conventional anatomic imaging modalities and contemporary invasive tissue acquisition techniques. Given the key and expanding role of precision imaging in radiation oncology for patient selection, target delineation, image guided treatment delivery, and response assessment, noninvasive molecular-specific imaging may be uniquely suited to evaluate radiation/immunotherapy combinations. Herein, we describe several experimental imaging-based strategies that are currently being explored to characterize in vivo immune responses, and we review a growing body of preclinical data and nascent clinical experience with immuno-positron emission tomography molecular imaging as a putative biomarker for cancer immunotherapy. Finally, we discuss practical considerations for clinical translation to implement noninvasive molecular imaging of immune checkpoint molecules, immune cells, or associated elements of the antitumor immune response with a specific emphasis on its potential application at the interface of radiation oncology and immuno-oncology.
免疫疗法与放射肿瘤学的交叉领域是临床前和临床研究中一个快速发展的领域。将放射疗法和免疫疗法相结合以增强局部和全身抗肿瘤免疫反应的策略很有吸引力，但在临床环境中很大程度上尚未得到证实，因为协同作用机制和治疗反应的决定因素仍不明确。近年来，几种非侵入性分子成像方法已成为探究肿瘤免疫微环境的平台。这些工具有可能作为癌症免疫疗法的强大生物标志物，并且可能比传统的解剖成像方式和当代侵入性组织采集技术具有多个优势。鉴于精准成像在放射肿瘤学中对于患者选择、靶区勾画、图像引导治疗实施和疗效评估的关键且不断扩大的作用，非侵入性分子特异性成像可能特别适合评估放射/免疫疗法的联合应用。在此，我们描述了目前正在探索的几种基于实验成像的策略，以表征体内免疫反应，并回顾了越来越多的临床前数据以及免疫正电子发射断层扫描分子成像作为癌症免疫疗法假定生物标志物的初步临床经验。最后，我们讨论了将免疫检查点分子、免疫细胞或抗肿瘤免疫反应相关元素的非侵入性分子成像应用于临床的实际考虑因素，特别强调其在放射肿瘤学与免疫肿瘤学交叉领域的潜在应用。
