精准靶向肿瘤局部的免疫治疗有可能成为治愈癌症的关键性策略

摘要]肿瘤免疫治疗的两大重要进展：（1）在体外激活或通过基因修饰的T细胞进行体内输注；（2）通过抗体使体内被抑制的免疫细胞激活并处于相对持续作用状态。前者的基因修饰的T细胞主要是指嵌合抗原受体T（CAR-T）细胞，其对部分血液肿瘤产生了明显的疗效；后者主要指免疫检查点抗体，其对基因突变较多的肿瘤产生了明显的疗效。对于肿瘤患者而言，其肿瘤局部微环境的免疫抑制状态往往明显高于全身的免疫抑制状态。要将肿瘤局部微环境的免疫状况调整到正常或增强，全身用药时可能引发其它正常组织免疫反应过强，甚至导致严重损害，如间质性肺炎、急性心肌炎及严重肝损伤。本文通过总结肿瘤免疫微环境的形成和分类、肿瘤治疗和免疫治疗的发展历程，阐述靶向肿瘤微环境的重要性，提出了用自分泌抗体的CAR-T 细胞（白泽T细胞）高效精准靶向肿瘤局部，迅速提高肿瘤局部微环境的免疫功能，且有可能成为治愈癌症的关键策略。

Immunotherapy precise targeting tumour microenvironment will become a key strategy of curing cancer

Abstract] The most two advanced development in cancer immunotherapy: (1) Infusion with in vitro activated or gene-modified T cells; (2) Activation of suppressive immune cells by antibodies to exert cytotoxicity. The first one about gene-modified T cells is mainly referred to chimeric antigen receptor-T cells (CAR-T) that have shown the significant efficacy in some haematological malignancies.The latter one about immune checkpoint blockades takes effects on tumors with burden of gene mutations. For cancer patients, however,tumor microenvironment is suppressed highly more than the systemic immune. Normalizing or enhancing the local microenvironment by systemic activation of immune response may cause the overreaction in other normal tissues, even severe damage, for example interstitial lung diseases, acute myocarditis, and severe liver failure. This review summarizes the characterization and classification of tumor immune microenvironment, development of cancer treatment and immunotherapy, and elucidates the importance of targeting tumor immune microenvironment. The key strategy is pointed out to efficiently and precision target tumor immune microenvironment by using self-secreting antibody CAR-T cells (baize T cells), quickly enhancing the immune function in tumor microenvironment, which may eventually cure cancer.