实体瘤局部免疫治疗的探索与发展现状

免疫治疗已被证实为极具前景的晚期恶性实体瘤治疗方式之一。肿瘤所致免疫激活和免疫效应主要来自肿瘤抗原与肿瘤微环境（tumor microenvironment，TME）的相互作用，而肿瘤抗原的免疫原性减弱与免疫应答通路缺陷是产生免疫逃逸的主要原因。免疫治疗通过不同途径增强抗原提呈能力，激活免疫应答及改善TME的免疫抑制状态，提高患者生存获益。由于免疫治疗疗效与药物浓度呈正相关，往往较高的治疗剂量才有效，但这对机体将造成不同程度的免疫相关毒性反应及诱导耐药产生。因此，一种新的治疗方式-局部免疫治疗，被探索并取得了早期临床疗效。本文就几种常见的不同类型免疫药物在局部治疗中的作用机制、应用特点及临床发展现状进行综述。 

Exploration and development of local immunotherapy for solid tumors

Immunotherapy has been proved to be one of the most promising treatments for advanced malignant solid tumors.It was found that the immune activation and immune effect caused by tumors mainly came from the interaction between tumor antigens and tumor microenvironment(TME),and the weakened immunogenicity of tumor antigens and the deficiency of immune response pathway were the main causes for immune escaping.Immunotherapy is able to enhance the ability of antigen presentation,activate the immune response and improve the immunosuppressive status of TME via different ways,and then,improving the survival benefits.Whereas,the effect of immunotherapy is positively correlated with the drug concentration-a higher therapeutic dose is often effective,which will cause different degree of immune-related toxicities and even induce drug resistance in vivo.Therefore,a new treatment method,local immunotherapy,aiming to elevate local drug concentrationhas but with a good tolerance,has been explored and gotten an early clinical efficacy.This article will describe the activated mechanisms,application characteristics and clinical development of several immune drugs using in locally.