目前，针对程序性细胞死亡配体-1 (PD-L1) 的免疫检查点阻断 (ICB) 疗法已在临床上用作革命性的癌症治疗方法。除了通过阻断肿瘤细胞上的 PD-L1 与 T 细胞上的程序性细胞死亡 1 (PD-1) 之间的相互作用来恢复细胞毒性 T 细胞的抗肿瘤反应外，PD-L1 蛋白还被新发现具有加速细胞毒性 T 细胞抗肿瘤反应的能力。 DNA损伤修复（DDR）并通过多种机制促进肿瘤生长，导致肿瘤治疗效果受损。然而，目前的免费抗PD-1/PD-L1疗法在大多数实体瘤中仍然因非选择性肿瘤积累、不可避免的严重细胞毒性作用以及普遍发生的免疫抵抗而导致治疗效果不佳。最近，具有高效肿瘤靶向能力、肿瘤响应繁荣和联合治疗多功能性的纳米粒子被认为是 PD-L1 靶向癌症免疫疗法的新途径。在这篇综述中，我们首先总结了PD-L1蛋白在促进肿瘤生长、加速DDR以及抑制免疫治疗疗效方面的多种功能。随后，讨论了当前临床广泛使用的肿瘤治疗对肿瘤PD-L1表达的影响和机制。然后，我们回顾了通过使用PD-L1抗体、小干扰RNA（siRNA）、微小RNA（miRNA）、成簇、规则间隔、短回文重复序列（CRISPR）、肽和纳米粒子用于抗PD-L1治疗的最新进展。小分子药物。最后，我们讨论了促进基于纳米颗粒的 PD-L1 靶向治疗临床应用的挑战和前景。版权所有 © 2023。由 Elsevier B.V. 出版。

Currently, immune checkpoint blockade (ICB) therapies that target the programmed cell death ligand-1 (PD-L1) have been used as revolutionary cancer treatments in the clinic. Apart from restoring the antitumor response of cytotoxic T cells by blocking the interaction between PD-L1 on tumor cells and programmed cell death-1 (PD-1) on T cells, PD-L1 proteins were also newly revealed to possess the capacity to accelerate DNA damage repair (DDR) and enhance tumor growth through multiple mechanisms, leading to the impaired efficacy of tumor therapies. Nevertheless, current free anti-PD-1/PD-L1 therapy still suffered from poor therapeutic outcomes in most solid tumors due to the non-selective tumor accumulation, ineludible severe cytotoxic effects, as well as the common occurrence of immune resistance. Recently, nanoparticles with efficient tumor-targeting capacity, tumor-responsive prosperity, and versatility for combination therapy were identified as new avenues for PD-L1 targeting cancer immunotherapies. In this review, we first summarized the multiple functions of PD-L1 protein in promoting tumor growth, accelerating DDR, as well as depressing immunotherapy efficacy. Following this, the effects and mechanisms of current clinically widespread tumor therapies on tumor PD-L1 expression were discussed. Then, we reviewed the recent advances in nanoparticles for anti-PD-L1 therapy via using PD-L1 antibodies, small interfering RNA (siRNA), microRNA (miRNA), clustered, regularly interspaced, short palindromic repeats (CRISPR), peptide, and small molecular drugs. At last, we discussed the challenges and perspectives to promote the clinical application of nanoparticles-based PD-L1-targeting therapy.Copyright © 2023. Published by Elsevier B.V.