The complex role of PD-L1 in antitumor immunity: a recent update
The complex role of PD-L1 in antitumor immunity: a recent update
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DOI：
10.1038/s41423-021-00702-y
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发表时间：
2021-05
影响因子：
24.1
通讯作者：
Xiaoqing Zhang;Y. Huang;Xuanming Yang
中科院分区：
文献类型：
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作者：
Xiaoqing Zhang;Y. Huang;Xuanming Yang
PD-1是免疫球蛋白基因超家族的一员，被发现参与程序性细胞死亡，随后被证明对T细胞的负调控至关重要。其配体PD-L1 （B7-H1）和PD-L2 （B7-DC）与PD-1相互作用，负向调节T细胞介导的免疫应答。CD80也作为一种反受体与PD-L1相互作用。此外，PD-L1可以作为受体向T细胞和肿瘤细胞传递信号，抵抗免疫介导的破坏。因此，PD-L1可以作为免疫调节功能的配体和受体。本文将重点讨论PD-L1的各种细胞来源在调节抗肿瘤免疫中的作用。除肿瘤细胞外，活化的免疫细胞，如T细胞、B细胞和自然杀伤（NK）细胞也常表达PD-L1。1 PD-L1也常在肿瘤微环境中的骨髓细胞上表达，包括巨噬细胞、髓源性抑制细胞和树突状细胞（dc）。1 PDL1的表达在肿瘤细胞和正常细胞中均可被多种细胞因子上调，尤其是干扰素-γ。1 pdl1表达细胞对抗肿瘤T细胞抑制的贡献对于区分患者对抗pd -1/PD-L1免疫治疗的反应以及详细了解PD-L1介导的抑制机制至关重要。在发现PD-1在自身免疫性疾病中的抑制作用后不久，1在同基因肿瘤模型中发现肿瘤细胞中异位表达的PDL1具有T细胞抑制作用。2-4随后，肿瘤细胞上的PD-L1被广泛用作检查点阻断治疗的生物标志物或伴随诊断。然而，几乎一半肿瘤PD-L1表达阳性的患者没有反应，而一些PD-L1阴性的肿瘤患者仍然对PD-L1阻断有反应，这表明PD-1/PDL1信号传导如何影响免疫反应的工作模型可能更为复杂。5因此，近年来大量的研究集中在探索不同细胞来源的PD-L1的重要作用。Kleinovink等人、Munn等人以及Tang等人的研究表明，宿主细胞上PD-L1的表达对于PD-L1介导的T细胞抑制至关重要。6-8然而，Juneja等人发现肿瘤细胞上的PD-L1足以导致免疫逃逸。9 Noguchi et al.和Lau et al.认为肿瘤细胞PD-L1和宿主细胞PDL1都需要介导抗肿瘤抑制
PD-1, a member of the immunoglobulin gene superfamily, was found to be involved in programmed cell death and subsequently demonstrated to be critical for the negative regulation of T cells. Its ligands PD-L1 (B7-H1) and PD-L2 (B7-DC) interact with PD-1 and negatively regulate T cell-mediated immune responses. 1 CD80 also interacts with PD-L1 as a counterreceptor. Moreover, PD-L1 can serve as a receptor to transmit signals to T cells and tumor cells to resist immune-mediated destruction. 1 Therefore, PD-L1 can act as both a ligand and a receptor for immunoregulatory functions. This commentary will focus on the roles of various cellular sources of PD-L1 in regulating antitumor immunity. In addition to tumor cells, activated immune cells, such as T cells, B cells, and natural killer (NK) cells, often express PD-L1. 1 PD-L1 is also commonly expressed on myeloid cells, including macrophages, myeloid-derived suppressor cells, and dendritic cells (DCs), in the tumor microenvironment. 1 The expression of PDL1 can be upregulated in both tumor cells and normal cells by many cytokines, especially interferon-γ. 1 The contribution of PDL1-expressing cells to antitumor T cell suppression is critical for stratifying patients for their response to anti-PD-1/PD-L1 immunotherapy and for understanding PD-L1-mediated inhibitory mechanisms in detail.Soon after the discovery of the inhibitory role of PD-1 in autoimmune disease, 1 it was found that ectopically expressed PDL1 in tumor cells played a T cell-inhibitory role in a syngeneic tumor model. 2–4 Subsequently, PD-L1 on tumor cells has been widely used as a biomarker or companion diagnostic for checkpoint blockade therapy. However, almost half of patients positive for tumor PD-L1 expression fail to respond, while some patients with PD-L1-negative tumors still respond to PD-L1 blockade, suggesting that the working model of how PD-1/PDL1 signaling affects immune responses might be more complicated. 5 Therefore, in recent years, numerous studies have focused on exploring the important roles of PD-L1 from different cell sources. Kleinovink et al., Munn et al., and Tang et al. showed that PD-L1 expression on host cells is essential for PD-L1-mediated T cell suppression. 6–8 However, Juneja et al. revealed that PD-L1 on tumor cells is sufficient for immune evasion. 9 Noguchi et al. and Lau et al. concluded that both tumor cell PD-L1 and host cell PDL1 are required to mediate the suppression of antitumor