Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade.
Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade.
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DOI：
10.1016/j.ccell.2016.02.004
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发表时间：
2016-03-14
期刊：
影响因子：
50.3
通讯作者：
Fu YX
中科院分区：
文献类型：
--
作者：
Tang H;Wang Y;Chlewicki LK;Zhang Y;Guo J;Liang W;Wang J;Wang X;Fu YX
免疫检查点阻断治疗在大多数癌症患者中未能诱导应答，因此如何提高客观应答率成为一个紧迫的挑战。在这里，我们证明充分的T细胞在肿瘤组织中的渗透是对PD-L1阻断的反应的先决条件。以肿瘤坏死因子超家族成员LIGH靶向肿瘤，激活淋巴毒素β受体信号，导致产生趋化因子，招募大量T细胞。此外，通过抗体引导光靶向非T细胞炎症的肿瘤组织，创造了T细胞炎症的微环境，并克服了肿瘤对检查点封锁的抵抗力。我们的数据表明，靶向光线可能是一种有效的策略，可以提高非T细胞炎症肿瘤对检查点阻断和其他免疫疗法的反应。
Immune checkpoint blockade therapies fail to induce responses in 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 beta 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 indicates that targeting LIGHT might be a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors.