基于PD-L1分布和功能的癌症免疫治疗优化。
Optimization of Cancer Immunotherapy on the Basis of PD-L1 Distribution and Function.
发表日期:2023 Feb 12
作者:
Wei Zou, Xin Luo, Mengyuan Gao, Chang Yu, Xueting Wan, Suyun Yu, Yuanyuan Wu, Aiyun Wang, William Fenical, Zhonghong Wei, Yang Zhao, Yin Lu
来源:
BRITISH JOURNAL OF PHARMACOLOGY
摘要:
编程细胞死亡蛋白1(PD-1)/编程死亡配体1(PD-L1)免疫检查点阻断作为癌症免疫治疗的突破已展现出前所未有的积极成果。然而,PD-L1抗体的总体有效性不如预期。越来越多的研究表明,PD-L1不仅广泛分布和表达于细胞膜上,还存在于肿瘤细胞分泌的细胞外囊泡和细胞内。内源性和外源性PD-L1对影响抗肿瘤免疫治疗的疗效起着重要作用。在此,我们主要关注PD-L1的分布和功能,并进一步总结了潜在的靶向治疗策略。更重要的是,除了将PD-L1的总体表达丰度作为选择相应PD-1/PD-L1单克隆抗体(mAbs)的预测指标外,我们还提出,基于PD-L1不同分布的个性化联合治疗值得越来越多的关注,以在癌症患者中取得更高效和有效的治疗结果。本文受版权保护。保留所有权利。
Programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immune checkpoint blockade as a breakthrough in cancer immunotherapy has shown unprecedented positive outcomes in clinic. However, the overall effectiveness of PD-L1 antibody is less than expected. An increasing number of studies have demonstrated that PD-L1 is widely distributed and expressed not only on the cell membrane but also inside the cells as well as the extracellular vesicles secreted by tumor cells. Both endogenous and exogenous PD-L1 play significant roles in influencing the therapeutic effect of anti-tumor immunity. Herein, we mainly focused on the distribution and function of PD-L1 and further summarized the potential targeted therapeutic strategies. More importantly, in addition to taking the overall expression abundance of PD-L1 as a predictive indicator for selecting corresponding PD-1/PD-L1 monoclonal antibodies (mAbs), we also proposed that personalized combination therapies based on the different distribution of PD-L1 are worth gaining growing attention to achieve more efficient and effective therapeutic outcomes in cancer patients.This article is protected by copyright. All rights reserved.