Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, Michigan.
Cancer Res. 2021 Oct 15;81(20):5141-5143. doi: 10.1158/0008-5472.CAN-21-2926.
Immune checkpoint blockade involves the targeted antagonism of immunosuppressive interactions between antigen-presenting cells and/or tumor cells and effector T cells. Blockade of B7-H1, also known as programmed death-ligand 1 (PD-L1), prevents the ligation of inhibitory PD-L1 molecules to programmed cell death receptor 1 (PD-1) on T cells, engendering a potentiated response of tumor-specific T cells against tumor cells. In a article, Hirano and colleagues showed that T-cell-mediated tumor immunity becomes impaired when tumor cells interact with T cells via PD-L1 in the mouse tumor microenvironment. They showed that targeting PD-L1 or PD-1 with mAbs increased tumor cell lysis by T cells and suggested that tumor PD-L1 forms a "shield" preventing tumor cell lysis. Alongside other original mouse and human studies, this work generated scientific rationales for a new generation of cancer treatment focused on targeting the inhibitory PD-1/PD-L1 signaling pathway in the tumor microenvironment..
免疫检查点阻断涉及针对抗原呈递细胞和/或肿瘤细胞与效应 T 细胞之间免疫抑制相互作用的靶向拮抗。阻断 B7-H1，也称为程序性死亡配体 1（PD-L1），可防止抑制性 PD-L1 分子与 T 细胞上的程序性细胞死亡受体 1（PD-1）的结合，从而增强针对肿瘤细胞的肿瘤特异性 T 细胞的反应。在一篇文章中，Hirano 及其同事表明，当肿瘤细胞在小鼠肿瘤微环境中通过 PD-L1 与 T 细胞相互作用时，T 细胞介导的肿瘤免疫会受到损害。他们表明，用 mAb 靶向 PD-L1 或 PD-1 可增加 T 细胞对肿瘤细胞的裂解，并表明肿瘤 PD-L1 形成了一个“盾牌”，防止肿瘤细胞裂解。与其他原始的小鼠和人类研究一起，这项工作为新一代专注于靶向肿瘤微环境中抑制性 PD-1/PD-L1 信号通路的癌症治疗提供了科学依据。
