Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Cancer Res. 2018 Mar 15;78(6):1379-1382. doi: 10.1158/0008-5472.CAN-17-3607. Epub 2018 Feb 13.
Equilibrium between immune activation and suppression may be necessary to maintain immune homeostasis, because proinflammatory effector T cells (defined as antiregulatory T cells) counteract the functions of regulatory immune cells. These self-reactive T cells recognize human leukocyte antigen (HLA)-restricted epitopes derived from proteins expressed by regulatory immune cells such as IDO, PD-L1, PD-L2, or arginase. The activation of such proinflammatory effector T cells offers a novel way to directly target the tumor microenvironment, potentially giving them considerable clinical value, especially in patients with cancer. Vaccination against genetically stable cells with regular HLA expression is an attractive way to directly target immunosuppressive cells in addition to attracting proinflammatory cells into the tumor microenvironment. Importantly, vaccination toward IDO or PD-L1 to potentiate such T cells have proven safe, with minimal toxicity in the clinical phase I trials conducted thus far..
免疫激活和抑制之间的平衡可能对于维持免疫稳态是必要的，因为促炎效应 T 细胞（定义为负向调节性 T 细胞）对抗调节性免疫细胞的功能。这些自身反应性 T 细胞识别人类白细胞抗原（HLA）限制性表位，这些表位来源于调节性免疫细胞表达的蛋白质，如 IDO、PD-L1、PD-L2 或精氨酸酶。这种促炎效应 T 细胞的激活提供了一种直接靶向肿瘤微环境的新方法，可能具有相当大的临床价值，特别是在癌症患者中。针对具有常规 HLA 表达的基因稳定细胞的疫苗接种是一种有吸引力的方法，除了将促炎细胞吸引到肿瘤微环境中外，还可以直接靶向抑制性细胞。重要的是，针对 IDO 或 PD-L1 的疫苗接种以增强这种 T 细胞已被证明是安全的，迄今为止进行的临床 I 期试验中毒性最小。
