尽管 CTLA-4 和 PD1 等检查点分子几年前就已被描述，但 Nivolumab（一种抗 PD-1 抗体）等检查点抑制剂最近才被用于治疗经典霍奇金淋巴瘤 (cHL)。多项研究表明纳武单抗对 cHL 具有令人信服的治疗效果。然而，纳武单抗在 cHL 中的作用机制尚不完全清楚。本研究的目的是监测 cHL 体外模型以及天然增生性淋巴组织和 cHL 天然人体组织给予 Nivolumab 后细胞运动和细胞接触的变化。在组织和体外，纳武单抗孵育后，CD4+、CD8+、CD30+和CD20+细胞速度均保持不变。相比之下，在原代cHL组织中，Nivolumab治疗5小时后CD4 T细胞与HRS细胞之间的细胞接触持续时间显着增加，并且CD4 T细胞与HRS细胞的接触次数也略有增加（不显着），这表明 CD4 T 细胞特别有助于纳武单抗治疗所观察到的细胞毒性。纳武单抗孵育后，增生性淋巴组织中细胞接触的持续时间没有变化。总之，我们通过对天然淋巴瘤组织进行成像，首次表明在给予纳武单抗后，cHL 中 CD4 T 细胞和 HRS 细胞的相互作用增强。

Although checkpoint molecules like CTLA-4 and PD1 have been described several years ago, checkpoint inhibitors such as Nivolumab (an anti-PD-1 antibody) have only recently been used to treat classic Hodgkin lymphoma (cHL). Several studies have shown convincing therapeutic effects of Nivolumab in cHL. However, the mechanism of action of Nivolumab in cHL is not fully understood. The aim of this study was to monitor changes in cell motility and cell contacts after administration of Nivolumab to an in vitro model of cHL as well as to native hyperplastic lymphoid tissue and native human tissue from cHL. In both tissue and in vitro, CD4+, CD8+, CD30+ and CD20+ cell velocities were unchanged after Nivolumab incubation. In contrast, in primary cHL tissue, the duration of cell contacts between CD4+ T cells and HRS cells was significantly increased after 5 h Nivolumab treatment, and the number of contacts with HRS cells was also slightly increased for CD4+ T cells (not significant), suggesting that CD4+ T cells in particular contribute to the cytotoxicity observed as a result of Nivolumab therapy. There was no change in the duration of cell contacts in the hyperplastic lymphoid tissue after Nivolumab incubation. In conclusion, we show here for the first time by imaging of native lymphoma tissue an enhanced interaction of CD4+ T cells and HRS cells in cHL after Nivolumab administration.