Fan Timothy M, Selting Kimberly A
Comparative Oncology Research Laboratory, Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign Urbana, IL, United States.
Front Oncol. 2019 Jan 15;8:680. doi: 10.3389/fonc.2018.00680. eCollection 2018.
Radiotherapy serves as a foundational pillar for the therapeutic management of diverse solid tumors through the generation of lethal DNA damage and induction of cell death. While the direct cytotoxic effects of radiation therapy remain a cornerstone for cancer management, in the era of immunooncology there is renewed and focused interest in exploiting the indirect bystander activities of radiation, termed abscopal effects. In radioimmunobiologic terms, abscopal effects describe the radiotherapy-induced regression of cancerous lesions distant from the primary site of radiation delivery and rely upon the induction of immunogenic cell death and consequent systemic anticancer immune activation. Despite the promise of radiation therapy for awaking potent anticancer immune responses, the purposeful harnessing of abscopal effects with radiotherapy remain clinically elusive. In part, failure to fully leverage and clinically implement the promise of radiation-induced abscopal effects stems from limitations associated with existing conventional tumor models which inadequately recapitulate the complexity of malignant transformation and the dynamic nature of tumor immune surveillance. To supplement this existing gap in modeling systems, pet dogs diagnosed with solid tumors including melanoma and osteosarcoma, which are both metastatic and immunogenic in nature, could potentially serve as unique resources for exploring the fundamental underpinnings required for maximizing radiation-induced abscopal effects. Given the spontaneous course of cancer development in the context of operative immune mechanisms, pet dogs treated with radiotherapy for metastatic solid tumors might be leveraged as valuable model systems for realizing the science and best clinical practices necessary to generate potent abscopal effects with anti-metastatic immune activities.
放射治疗通过产生致命的DNA损伤和诱导细胞死亡，成为多种实体瘤治疗管理的基础支柱。虽然放射治疗的直接细胞毒性作用仍然是癌症治疗的基石，但在免疫肿瘤学时代，人们对利用放射的间接旁观者效应（即远隔效应）重新产生了浓厚兴趣并给予了重点关注。从放射免疫生物学角度来看，远隔效应描述的是放射治疗诱导远离放射原发部位的癌性病变消退，这依赖于免疫原性细胞死亡的诱导以及随之而来的全身抗癌免疫激活。尽管放射治疗有望引发强大的抗癌免疫反应，但在临床上，有目的地利用放射治疗的远隔效应仍然难以实现。部分原因在于，未能充分利用并在临床上实现放射诱导远隔效应的前景，这源于现有传统肿瘤模型的局限性，这些模型无法充分概括恶性转化的复杂性和肿瘤免疫监视的动态性质。为了弥补建模系统中这一现有的差距，被诊断患有包括黑色素瘤和骨肉瘤在内的实体瘤的宠物狗，这两种肿瘤本质上都是转移性和免疫原性的，它们有可能作为独特的资源，用于探索最大化放射诱导远隔效应所需的基本原理。考虑到在手术免疫机制背景下癌症发展的自然过程，接受放射治疗的转移性实体瘤宠物狗可能被用作有价值的模型系统，以实现产生具有抗转移免疫活性的强大远隔效应所需的科学和最佳临床实践。
