Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Avenue, Changchun, 130021, Jilin, China.
Cancer Immunol Immunother. 2020 May;69(5):789-797. doi: 10.1007/s00262-020-02500-3. Epub 2020 Feb 13.
CD160 is an Ig-like glycoprotein expressed by the majority of circulating natural killer cells and γδ T cells. Whether CD160 could regulate CD8 T-cell functions remains unknown. In this study, we investigated the effects of CD160 on CD8 T cells in pancreatic cancer. First, we found that the frequency of PD-1 cells was comparable between CD160 and CD160CD8 T cells, with the former presenting significantly higher PD-1 expression level. In contrast, the frequency of TIM-3 cells was higher among CD160 cells but the expression level was comparable between CD160 and CD160CD8 T cells. The IFN-γ and IL-2-expressing CD8 T cells, directly ex vivo, were highly enriched in the CD160 subset. However, when CD160 and CD160CD8 T cells were stimulated, the proliferation levels of CD160 and CD160 cells were initially comparable, but were significantly lower in CD160CD8 T cells than in CD160CD8 T cells later on. The IFN-γ and IL-2 transcription levels were initially higher in CD160CD8 T cells, but eventually reduced in CD160CD8 T cells compared to CD160CD8 T cells. Also, CD160CD8 T cells presented lower cytotoxic capacity than CD160CD8 T cells. Interestingly, we observed that tumor-infiltrating CD8 T cells were significantly enriched with the CD160 subset in pancreatic cancer patients. In addition, patients with higher frequencies of tumor CD160CD8 T cells presented lower survival. Overall, these data demonstrated that tumor-infiltrating CD8 T cells were enriched with the CD160 subset in pancreatic cancer, with active effector responses directly ex vivo but limited potential for further activation.
CD160 是一种 Ig 样糖蛋白，大多数循环自然杀伤细胞和 γδ T 细胞均表达 CD160。CD160 是否能调节 CD8 T 细胞功能尚不清楚。在这项研究中，我们研究了 CD160 对胰腺癌中 CD8 T 细胞的影响。首先，我们发现 PD-1 细胞的频率在 CD160 和 CD160CD8 T 细胞之间相当，前者表现出明显更高的 PD-1 表达水平。相比之下，CD160 细胞中 TIM-3 细胞的频率更高，但 CD160 和 CD160CD8 T 细胞之间的表达水平相当。IFN-γ 和 IL-2 表达的 CD8 T 细胞在 CD160 亚群中高度富集。然而，当刺激 CD160 和 CD160CD8 T 细胞时，CD160 和 CD160 细胞的增殖水平最初相当，但在 CD160CD8 T 细胞中后来明显低于 CD160CD8 T 细胞。IFN-γ 和 IL-2 的转录水平在 CD160CD8 T 细胞中最初较高，但最终在 CD160CD8 T 细胞中低于 CD160CD8 T 细胞。此外，CD160CD8 T 细胞的细胞毒性能力低于 CD160CD8 T 细胞。有趣的是，我们观察到在胰腺癌患者中，肿瘤浸润的 CD8 T 细胞明显富集于 CD160 亚群。此外，肿瘤中 CD160CD8 T 细胞频率较高的患者生存时间较短。总的来说，这些数据表明在胰腺癌中，肿瘤浸润的 CD8 T 细胞富集于 CD160 亚群，具有直接的效应器反应，但进一步激活的潜力有限。
