树突状细胞 (DC) 在肿瘤微环境中表达高水平的 PD-L1。然而，PD-L1 在 DC 上的生理功能仍不完全清楚。在这里，我们探讨了 PD-L1 信号在免疫原性化疗中的作用。我们发现，如果 DC 上缺乏 PD-L1，抗肿瘤功效会显着降低。化疗重塑了肿瘤免疫微环境，特别是 DC 区室。在缺乏 PD-L1 的情况下，DC 更容易受到化疗引起的细胞毒性的影响。从机制上讲，PD-L1 的缺失导致 SLC7A11 下调，导致脂质过氧化增加，导致 DC 屈服于铁死亡并抑制抗肿瘤免疫反应。具有 Pdl1 缺陷的 DC 的小鼠在化疗期间启动 T 细胞的效率较低。在癌症患者中，DC 上较高水平的 PD-L1 与免疫原性化疗后较好的预后相关。总的来说，这些发现揭示了 PD-L1 在协调 DC 存活中的作用未被充分认识，这在化学免疫治疗期间至关重要。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Dendritic cells (DCs) express high levels of PD-L1 in the tumor microenvironment. However, the physiological functions of PD-L1 on DCs remain incompletely understood. Here, we explored the roles of PD-L1 signaling during immunogenic chemotherapy. We found that antitumor efficacy was dramatically reduced in the absence of PD-L1 on DCs. Chemotherapy reshaped the tumor immune microenvironment, particularly the DC compartment. In the absence of PD-L1, DCs were more susceptible to the cytotoxicity induced by chemotherapy. Mechanistically, loss of PD-L1 led to the downregulation of SLC7A11, resulting in increased lipid peroxidation that caused DCs to succumb to ferroptosis and dampened antitumor immune responses. Mice with Pdl1-deficient DCs were less efficient at priming T cells during chemotherapy. In cancer patients, a higher level of PD-L1 on DCs correlated with better prognosis after immunogenic chemotherapy. Collectively, these findings reveal an underappreciated role of PD-L1 in orchestrating DC survival, which is critical during chemoimmunotherapy.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.