针对免疫检查点的阻断是众多激活抗肿瘤免疫的有效策略之一。免疫检查点是指免疫系统中存在的一些抑制性信号通路，通过调节外周组织中免疫反应的持续性和强度避免组织损伤，并参与维持对于自身抗原的耐受。利用免疫检查点的抑制性信号通路抑制T细胞活性是肿瘤逃避免疫杀伤的重要机制。细胞毒性T淋巴细胞相关抗原-4（cytotoxic T lymphocyte-associated antigen-4，CTLA-4）抗体Ipilimumab是首个被美国FDA批准靶向免疫检查点的治疗药物，对其他的免疫检查点如程序性死亡蛋白-1（programmed death protein-1，PD-1）及其配体的抑制能够有效治疗多种肿瘤，而且能诱发持续的肿瘤缓解。靶向免疫检查点在抗肿瘤免疫治疗中有着广阔的应用前景，由于经典的化疗药物具有免疫调节作用，使得免疫治疗与化疗的联合成为新的趋势。%The blockade of targeted immune checkpoint is one of the most promising approaches to activate therapeutic antitu-mor immunity. The immune checkpoint refers to a plethora of inhibitory pathways in the immune system. These pathways are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues to minimize collateral tissue damage. Tumors co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance. Cytotoxic T-lymphocyte-associated antigen 4 antibodies were the first of this class of immunotherapeutics to acquire approval from the US Food and Drug Administration. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as pro-grammed cell death protein 1, indicate broad and diverse opportunities to enhance anti-tumor immunity with the potential to produce du-rable clinical responses. Classic chemotherapy exerts significant immunomodulatory effects on tumor cells via multiple mechanisms. Therefore, the combination of immunotherapy, including immune checkpoint blockade with chemotherapy, is a new promising trend in anti-tumor immunotherapy.
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