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肿瘤抗原特异性T细胞的功能受到正向和负向两方面的信号调节。肿瘤能够诱导T细胞无能,其主要原因是由于缺乏积极的正向刺激信号,而使得负调免疫机制占主导地位。T细胞上程序死亡分子1(PD-1)的高表达,并与肿瘤细胞的PD-1配体之一(PD-L1)分子相互作用介导了T细胞功能耗竭状态,这是其中非常重要的负调信号通路。临床前癌症模型中,阻断PD-1/PD-L1的相互作用,可以提高抗肿瘤的T细胞反应,进而控制肿瘤进程。目前,靶向PH-1和PD-L1单克隆抗体药物的开发已经取得了非常好的研究进展,并在多种癌症患者的Ⅰ/Ⅱ期临床试验评估中取得了理想的治疗效果。所以,抑制负向免疫调节途径的相关药物的研发,也就成为潜在的、非常有价值的肿瘤免疫治疗方式。
Tumor antigen-specific T cell function is positively and negatively regulated by both signals. Tumor cells can induce inability of T cells, the main reason is due to the lack of a positive signal of positive stimuli, making the negative tone immune system dominance. It is very important that the high expression of PD-1 on T cells and the PD-1 ligand molecule (PD-L1) molecule of tumor cells mediate T cell depletion Negative tone signal path. In preclinical cancer models, blocking the PD-1 / PD-L1 interaction enhances the anti-tumor T cell response and thus the tumor progression. At present, the development of drugs targeting PH-1 and PD-L1 monoclonal antibodies has achieved very good research progress and has achieved the desired therapeutic effect in the phase I / II clinical trial evaluation of a variety of cancer patients. Therefore, the development of drugs that inhibit the negative immunomodulatory pathways has also become a potential and valuable tumor immunotherapy.