Department of Hepatobiliary Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Immunol Res. 2020 Dec;68(6):436-444. doi: 10.1007/s12026-020-09155-3. Epub 2020 Sep 25.
It is recently shown that PD-1 expression by immune cells of the myeloid lineage contributes to the suppression of antitumor immunity. The expression of PD-1 by antigen-presenting cells in hepatocellular carcinoma (HCC), a malignancy with high intratumoral PD-L1 expression, remained understudied. Here, we found that circulating monocytes from HBV-associated HCC patients upregulated PD-1 in a severity-dependent manner. Monocyte stimulation using IFN-γ or high levels of IL-10 could slightly increase PD-1 expression, while LPS could markedly increase PD-1 expression. Interestingly, LPS in combination with IL-4 or IL-10 presented stronger stimulation of PD-1 expression than LPS in combination with IFN-γ or LPS alone. At resting state, PD-1 monocytes presented comparable MHC-I and IL-12 expression and higher MHC-II, CD86, iNOS, arginase I, and IL-10 expression than PD-1 monocytes. Upon LPS stimulation, PD-1 monocytes presented lower iNOS and higher arginase I and IL-10 expression than PD-1 monocytes, indicating an M2-polarization bias in PD-1 monocytes. CD8 T cells following coculture with PD-1 monocytes presented lower IFN-γ and lower TNF-α expression, together with lower proliferation capacity, than CD8 T cells following coculture with PD-1 monocytes, suggesting that PD-1 monocytes were less capable of supporting CD8 T cell activation. Overall, these data indicated that PD-1 expression was elevated in monocytes from hepatocellular carcinoma patients. In addition, PD-1 monocytes presented a preference toward M2 polarization and had a deficiency in supporting CD8 T cells.
最近的研究表明，髓系免疫细胞表达 PD-1 有助于抑制抗肿瘤免疫。肝癌（HCC）是一种具有高肿瘤内 PD-L1 表达的恶性肿瘤，其抗原呈递细胞中 PD-1 的表达仍未得到充分研究。在这里，我们发现 HBV 相关 HCC 患者的循环单核细胞以严重程度依赖的方式上调 PD-1 的表达。IFN-γ或高浓度 IL-10 刺激单核细胞可轻微增加 PD-1 的表达，而 LPS 可显著增加 PD-1 的表达。有趣的是，LPS 与 IL-4 或 IL-10 联合使用比 LPS 与 IFN-γ 或 LPS 单独使用时对 PD-1 表达的刺激更强。在静息状态下，PD-1 单核细胞表现出相当的 MHC-I 和 IL-12 表达，以及更高的 MHC-II、CD86、iNOS、精氨酸酶 I 和 IL-10 表达，高于 PD-1 单核细胞。在 LPS 刺激下，PD-1 单核细胞表现出较低的 iNOS 和较高的精氨酸酶 I 和 IL-10 表达，与 PD-1 单核细胞相比，表明 PD-1 单核细胞存在 M2 极化偏向。与 PD-1 单核细胞共培养的 CD8 T 细胞表达的 IFN-γ 和 TNF-α较低，增殖能力较低，与与 PD-1 单核细胞共培养的 CD8 T 细胞相比，表明 PD-1 单核细胞在支持 CD8 T 细胞活化方面的能力较低。总的来说，这些数据表明 PD-1 在肝癌患者的单核细胞中表达上调。此外，PD-1 单核细胞表现出向 M2 极化的偏好，并且在支持 CD8 T 细胞方面存在缺陷。
