PD-1（程序性细胞死亡蛋白1）调节肿瘤微环境中骨髓源性抑制细胞的代谢重编程和骨髓细胞分化，以及骨髓细胞中的I型干扰素（IFN-I）信号通路。因此，PD-1 是骨髓细胞中的关键抑制性受体。然而，骨髓细胞中PD-1表达的调节尚不清楚。我们报道，编码PD-1蛋白的基因PDCD1的表达水平与人结直肠癌骨髓细胞中IFNB1和IFNAR1的水平呈正相关。用重组 IFNβ 蛋白处理小鼠骨髓细胞系可提高体外骨髓细胞中 PD-1 的表达。敲除编码 IFN-I 特异性受体的基因 IFNAR1，可在体外减弱 IFNβ 对骨髓细胞中 PD-1 表达的诱导作用。用脂质纳米颗粒封装的 IFNβ 编码质粒 (IFNBCOL01) 治疗荷瘤小鼠，IFNβ 表达增加，导致肿瘤浸润骨髓细胞中 PD-1 表达升高。在分子水平上，我们确定 IFNβ 会激活骨髓细胞中的 STAT1（信号转导子和转录激活子 1）和 IRF（干扰素调节因子）。对 cd279 启动子的分析鉴定了 IRF2 结合共有序列元件。 ChIP（染色质免疫沉淀）分析确定，在体外和体内骨髓细胞中，pSTAT1 直接结合 irf2 启动子，IRF2 直接结合 cd279 启动子。在结肠癌患者中，肿瘤浸润骨髓细胞中STAT1、IRF2和PDCD1的表达水平呈正相关。我们的研究结果确定，IFNβ 至少部分通过刺激骨髓细胞中的 pSTAT1-IRF2 轴，通过自分泌机制激活 PD-1 表达。

PD-1 (Programmed cell death protein 1) regulates the metabolic reprogramming of myeloid-derived suppressor cells and myeloid cell differentiation, as well as the type I interferon (IFN-I) signaling pathway in myeloid cells in the tumor microenvironment. PD-1, therefore, is a key inhibitory receptor in myeloid cells. However, the regulation of PD-1 expression in myeloid cells is unknown. We report that the expression level of PDCD1, the gene that encodes the PD-1 protein, is positively correlated with the levels of IFNB1 and IFNAR1 in myeloid cells in human colorectal cancer. Treatment of mouse myeloid cell lines with recombinant IFNβ protein elevated PD-1 expression in myeloid cells in vitro. Knocking out IFNAR1, the gene that encodes the IFN-I-specific receptor, diminished the inductive effect of IFNβ on PD-1 expression in myeloid cells in vitro. Treatment of tumor-bearing mice with a lipid nanoparticle-encapsulated IFNβ-encoding plasmid (IFNBCOL01) increased IFNβ expression, resulting in elevated PD-1 expression in tumor-infiltrating myeloid cells. At the molecular level, we determined that IFNβ activates STAT1 (signal transducer and activator of transcription 1) and IRFs (interferon regulatory factors) in myeloid cells. Analysis of the cd279 promoter identified IRF2-binding consensus sequence elements. ChIP (chromatin immunoprecipitation) analysis determined that the pSTAT1 directly binds to the irf2 promoter and that IRF2 directly binds to the cd279 promoter in myeloid cells in vitro and in vivo. In colon cancer patients, the expression levels of STAT1, IRF2 and PDCD1 are positively correlated in tumor-infiltrating myeloid cells. Our findings determine that IFNβ activates PD-1 expression at least in part by an autocrine mechanism via the stimulation of the pSTAT1-IRF2 axis in myeloid cells.