PD-1/PD-L1 axis represents an important target for renormalizing and resetting anti-tumor immunity in cancer patients. Currently, anti-PD-1/PD-L1 therapy has been applied in a broad spectrum of tumors and has yielded durable remission in patients. However, how to further broaden the application, guide personalized therapeutic strategies, and improve clinical responses remains a vital task. At present, PD-L1 expression is an important parameter of clinical indications for immune checkpoint blockade in many types of cancers, a strategy based on the supposition that positive PD-L1 expression reflects local T cell response. Recent studies have revealed that PD-L1 expression is regulated by multiple layers of complicated factors, during which the host immune microenvironment exerts a pivotal role and determines the clinical efficacy of the therapy. In this review, we will summarize recent findings on PD-1/PD-L1 in cancer, focusing on how local immune landscape participates in the regulation of PD-L1 expression and modification. Importantly, we will also discuss these topics in the context of clinical treatment and analyze how these fundamental principles might inspire our efforts to develop more precise and effective immune therapeutics for cancer.

PD-1/PD-L1轴代表了癌症患者抗肿瘤免疫重新正常化和重置的重要靶点。目前，抗PD-1/PD-L1疗法已广泛应用于多种肿瘤，并为患者带来了持久的缓解。然而，如何进一步拓宽应用范围、指导个性化治疗策略、提高临床反应仍然是至关重要的任务。目前，PD-L1表达是多种癌症中免疫检查点阻断临床指征的重要参数，该策略基于PD-L1阳性表达反映局部T细胞反应的假设。近年来的研究表明，PD-L1的表达受到多层次复杂因素的调控，其中宿主免疫微环境发挥着关键作用，决定了治疗的临床疗效。在这篇综述中，我们将总结癌症中 PD-1/PD-L1 的最新发现，重点关注局部免疫景观如何参与 PD-L1 表达和修饰的调节。重要的是，我们还将在临床治疗的背景下讨论这些主题，并分析这些基本原则如何激发我们开发更精确、更有效的癌症免疫疗法的努力。