Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Cell Immunol. 2021 Nov;369:104435. doi: 10.1016/j.cellimm.2021.104435. Epub 2021 Aug 29.
The PD-1/PD-L1 axis plays a crucial role in regulating the anti-tumour immune response. A soluble PD-1 protein (sPD-1) has previously been observed, which could block the binding of PD-L1 to PD-1. Tumour associated macrophages are abundant in tumours, and evidence suggest they express PD-1. However, whether they also express sPD-1 remains unclear. The objective of this study was to investigate expression of sPD-1 in two in vitro models of human macrophages: THP-1 cells and monocyte-derived macrophages (MDM). Cells were polarised with either LPS + IFN-γ or IL-4 + IL-13 or left unpolarised. PD-1 and sPD-1 mRNAs were measured using droplet digital PCR, sPD-1 protein by electrochemiluminescence immunoassay and PD-1 by flow cytometry. sPD-1 mRNA was induced in both THP-1 cells and MDM after polarisation with LPS + IFN-γ, while IL-4 + IL-13 induced sPD-1 mRNA in MDM only. sPD-1 protein was measurable in culture supernatants. These findings show that macrophages can be induced to express sPD-1.
PD-1/PD-L1 轴在调节抗肿瘤免疫反应中起着至关重要的作用。先前已经观察到可溶性 PD-1 蛋白（sPD-1），它可以阻断 PD-L1 与 PD-1 的结合。肿瘤相关巨噬细胞在肿瘤中大量存在，有证据表明它们表达 PD-1。然而，它们是否也表达 sPD-1尚不清楚。本研究的目的是研究两种体外人类巨噬细胞模型：THP-1 细胞和单核细胞衍生的巨噬细胞（MDM）中 sPD-1 的表达。用 LPS+IFN-γ或 IL-4+IL-13 极化细胞，或不极化。使用液滴数字 PCR 测量 PD-1 和 sPD-1 mRNA，使用电化学发光免疫测定法测量 sPD-1 蛋白，使用流式细胞术测量 PD-1。用 LPS+IFN-γ 极化后，THP-1 细胞和 MDM 中均可诱导 sPD-1 mRNA，而 IL-4+IL-13 仅在 MDM 中诱导 sPD-1 mRNA。可在培养上清液中测量 sPD-1 蛋白。这些发现表明巨噬细胞可以被诱导表达 sPD-1。
