Mayo Clinic, Rochester, MN
J Oncol Pract. 2016 Feb;12(2):101-6. doi: 10.1200/JOP.2015.009191.
Tumor-specific cytotoxic T cells have the capacity to target and eradicate malignant B cells in patients with Hodgkin and non-Hodgkin lymphoma; however, multiple mechanisms, including regulatory T cells, immunosuppressive ligands, and immune exhaustion, suppress an effective antitumor immune response. One mechanism that is used by malignant cells to inhibit the immune response is overexpression of programmed death ligand 1 or 2 (PD-L1 or PD-L2) on the cancer cell surface. These ligands interact with the programmed death-1 (PD-1) receptor expressed on intratumoral T cells and provide an inhibitory signal, thereby suppressing the antitumor immune response. Monoclonal antibodies that block PD-1 signaling prevent T-cell inhibition and promote a T-cell-mediated antilymphoma response. Blocking antibodies that are directed against PD-1 or PD-L1 are currently being tested in patients with lymphoma and have shown remarkable efficacy, particularly in patients with relapsed Hodgkin lymphoma. On the basis of the promising activity of this approach, PD-1 inhibitors are being used as single-agent therapy in patients with relapsed Hodgkin lymphoma, and these inhibitors are also being tested in combination with standard chemotherapy or targeted agents in ongoing clinical trials.
肿瘤特异性细胞毒性 T 细胞具有靶向和消除霍奇金和非霍奇金淋巴瘤患者恶性 B 细胞的能力；然而，多种机制，包括调节性 T 细胞、免疫抑制配体和免疫衰竭，抑制了有效的抗肿瘤免疫反应。恶性细胞用来抑制免疫反应的一种机制是在癌细胞表面过度表达程序性死亡配体 1 或 2（PD-L1 或 PD-L2）。这些配体与肿瘤内 T 细胞表达的程序性死亡受体-1（PD-1）相互作用，提供抑制信号，从而抑制抗肿瘤免疫反应。阻断 PD-1 信号的单克隆抗体可防止 T 细胞抑制，并促进 T 细胞介导的抗淋巴瘤反应。针对 PD-1 或 PD-L1 的阻断抗体目前正在淋巴瘤患者中进行测试，并显示出显著的疗效，尤其是在复发的霍奇金淋巴瘤患者中。基于这种方法的良好疗效，PD-1 抑制剂被用作复发的霍奇金淋巴瘤患者的单一治疗药物，并且这些抑制剂也正在临床试验中与标准化疗或靶向药物联合进行测试。
