Tumors frequently escape from immune surveillance by hijacking the natural control mechanisms that regulate normal immune responses. The programmed death-1 receptor (PD‑1) on T cells normally helps limit excessive immune activation, but it can also suppress beneficial antitumor immunity. In the clinic, blocking either PD‑1 or one of its principal counterligands, programmed death–ligand 1 (PD‑L1), can lead to dramatic responses in certain patients. Because PD‑L1 can be expressed by both the tumor cells themselves and also the host cells, including host immune cells, the actual mechanistic target of therapy has remained unclear. In the current issue of the JCI, two papers, one by Tang and colleagues and the other by Lin and colleagues, used a variety of mouse tumor models to demonstrate that the relevant target for therapy in each case was the PD‑L1 molecules expressed by host cells and not by tumor cells. If this finding is generalized to humans, then it would suggest that the tumor persuades the host to actively suppress its own attempted immune response against the tumor cells.

肿瘤经常通过劫持调节正常免疫反应的自然控制机制而逃避免疫监视。T细胞上编程的死亡1受体（PD-1）通常有助于限制过度的免疫激活，但它也可以抑制有益的抗肿瘤免疫力。在诊所中，阻断PD-1或其主要配体之一（程序性死亡配体1（PD‑L1））可能会导致某些患者发生剧烈反应。由于PD‑L1既可以由肿瘤细胞本身表达，也可以由宿主细胞（包括宿主免疫细胞）表达，因此尚不清楚实际的治疗靶点。在本期JCI中，有两篇论文，一份是唐和同事的，另一份是林和同事的，使用了多种小鼠肿瘤模型来证明每种情况下相关的治疗靶标是宿主细胞而非肿瘤细胞表达的PD‑L1分子。如果这一发现普遍适用于人类，则表明该肿瘤诱使宿主积极抑制自身针对肿瘤细胞的尝试性免疫反应。