Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Cancer Cell. 2016 Mar 14;29(3):285-296. doi: 10.1016/j.ccell.2016.02.004.
Immune checkpoint blockade therapies fail to induce responses in the majority of cancer patients, so how to increase the objective response rate becomes an urgent challenge. Here, we demonstrate that sufficient T cell infiltration in tumor tissues is a prerequisite for response to PD-L1 blockade. Targeting tumors with tumor necrosis factor superfamily member LIGHT activates lymphotoxin β-receptor signaling, leading to the production of chemokines that recruit massive numbers of T cells. Furthermore, targeting non-T cell-inflamed tumor tissues by antibody-guided LIGHT creates a T cell-inflamed microenvironment and overcomes tumor resistance to checkpoint blockade. Our data indicate that targeting LIGHT might be a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors.
免疫检查点阻断疗法未能在大多数癌症患者中诱导应答，因此如何提高客观缓解率成为一个迫切的挑战。在这里，我们证明了肿瘤组织中足够的 T 细胞浸润是对 PD-L1 阻断产生应答的前提条件。用肿瘤坏死因子超家族成员 LIGHT 靶向肿瘤可激活淋巴毒素 β 受体信号，导致募集大量 T 细胞的趋化因子的产生。此外，通过抗体引导 LIGHT 靶向非 T 细胞浸润的肿瘤组织会创建一个 T 细胞浸润的微环境，并克服肿瘤对检查点阻断的耐药性。我们的数据表明，靶向 LIGHT 可能是一种有效的策略，可以增加非 T 细胞浸润肿瘤对检查点阻断和其他免疫疗法的反应。
