School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Perth, WA 6102, Australia.
National Centre for Asbestos Related Diseases, UWA School of Medicine and Pharmacology, Harry Perkins Institute of Medical Research, QEII Medical Centre, Perth, WA, Australia.
J Immunol Res. 2014;2014:789069. doi: 10.1155/2014/789069. Epub 2014 May 18.
Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The "Trojan Horse" approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more "full frontal" treatments such as transfer of large numbers of laboratory-expanded tumor-specific cytotoxic T lymphocytes or large intravenous doses of cytokine. Numerous studies have demonstrated that intratumoural therapy has the capacity to minimizing local suppression, inducing sufficient "dangerous" tumor cell death to cross-prime strong immune responses, and rending tumor blood vessels amenable to immune cell traffic to induce effector cell changes in secondary lymphoid organs. However, the key to its success is the design of a sound rational approach based on evidence. There is compelling preclinical data for local immunotherapy approaches in tumor immunology. This review summarises how immune events within a tumour can be modified by local approaches, how this can affect systemic antitumor immunity such that distal sites are attacked, and what approaches have been proven most successful so far in animals and patients.
大多数癌症治疗方法包括免疫疗法都是全身性的；然而，直接给予肿瘤的治疗方法可能更有效，特别是那些克服肿瘤微环境中天然抑制因素的方法。肿瘤内递药的“特洛伊木马”方法旨在通过同时诱导肿瘤内微环境变化来促进免疫介导的破坏，同时避免与更“全面”治疗相关的全身毒性，例如大量实验室扩增的肿瘤特异性细胞毒性 T 淋巴细胞转移或大剂量细胞因子静脉内给药。许多研究表明，肿瘤内治疗具有最小化局部抑制、诱导足够“危险”的肿瘤细胞死亡以交叉引发强烈免疫反应以及使肿瘤血管易于免疫细胞运输以在次级淋巴器官中诱导效应细胞变化的能力。然而，其成功的关键是基于证据制定合理的合理方法。肿瘤免疫学中有大量令人信服的临床前局部免疫治疗方法的数据。这篇综述总结了肿瘤内的免疫事件如何通过局部方法进行修饰，这如何影响全身性抗肿瘤免疫以至于远处部位受到攻击，以及迄今为止在动物和患者中哪些方法最成功。
