Signaling between programmed cell death protein 1 (PD-1) and the PD-1 ligands (PD-L1, PD-L2) is essential for malignant Hodgkin Reed-Sternberg (HRS) cells to evade antitumor immunity in classical Hodgkin lymphoma (cHL). Copy number alterations of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) contribute to robust PD-L1 and PD-L2 expression by HRS cells. PD-L1 is also expressed by nonmalignant tumor-associated macrophages (TAMs), but the relationships among PD-L1+ HRS cells, PD-L1+ TAMs, and PD-1+ T cells remain undefined. We used multiplex immunofluorescence and digital image analysis to examine the topography of PD-L1+ and PD-1+ cells in the tumor microenvironment (TME) of cHL. We find that the majority of PD-L1 in the TME is expressed by the abundant PD-L1+ TAMs, which physically colocalize with PD-L1+ HRS cells in a microenvironmental niche. PD-L1+ TAMs are enriched for contacts with T cells, and PD-L1+ HRS cells are enriched for contacts with CD4+ T cells, a subset of which are PD-1+ Our data define a unique topology of cHL in which PD-L1+ TAMs surround HRS cells and implicate CD4+ T cells as a target of PD-1 blockade.

中文翻译：

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拓扑分析揭示了霍奇金淋巴瘤中 Reed-Sternberg 细胞的 PD-L1 相关微环境生态位

程序性细胞死亡蛋白 1 (PD-1) 和 PD-1 配体 (PD-L1、PD-L2) 之间的信号传导对于恶性霍奇金 Reed-Sternberg (HRS) 细胞逃避经典霍奇金淋巴瘤 (cHL) 中的抗肿瘤免疫至关重要. 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) 的拷贝数改变有助于 HRS 细胞稳健地表达 PD-L1 和 PD-L2。PD-L1 也由非恶性肿瘤相关巨噬细胞 (TAM) 表达，但 PD-L1+ HRS 细胞、PD-L1+ TAM 和 PD-1+ T 细胞之间的关系仍未确定。我们使用多重免疫荧光和数字图像分析来检查 cHL 肿瘤微环境 (TME) 中 PD-L1+ 和 PD-1+ 细胞的形貌。我们发现 TME 中的大部分 PD-L1 由丰富的 PD-L1+ TAM 表达，它们在微环境生态位中与 PD-L1+ HRS 细胞物理共定位。