Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients
Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients
复制标题
胃癌组织中程序性死亡受体1（PD-1）阳性巨噬细胞增多与胃癌患者预后不良密切相关。
DOI：
10.1186/s12885-020-6629-6
复制
发表时间：
2020-03-04
期刊：
影响因子：
3.8
通讯作者：
Fujiwara, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Kono, Yusuke;Saito, Hiroaki;Fujiwara, Yoshiyuki
背景程序性细胞死亡1(PD-1)是一种负向调节T细胞功能的免疫检查点分子。虽然最近的研究表明，PD-1也表达在T细胞以外的其他免疫细胞上，但其作用尚不清楚。本研究旨在探讨PD-1在巨噬细胞上的表达及其对胃癌患者抗肿瘤免疫功能的影响。方法用多色流式细胞术检测15例胃癌组织中PD-1(+)巨噬细胞的频率。同时采用PD-1和CD68免疫组织化学双重染色方法，探讨PD-1(+)巨噬细胞在胃癌患者中的表达频率与临床病理特征及预后的关系。结果胃癌组织中PD-1(+)巨噬细胞的表达频率明显高于非肿瘤胃组织。与PD-1(-)巨噬细胞相比，PD-1(+)巨噬细胞的吞噬功能严重受损。PD-1(+)巨噬细胞(低)和PD-1(+)巨噬细胞(高)患者的5年疾病特异性生存率分别为85.9%和65.8%(P=0.008)。多因素分析显示PD-1(+)巨噬细胞频率是一个独立的预后因素。结论PD-1(+)巨噬细胞功能严重受损，PD-1(+)巨噬细胞频率升高加重了GC患者的预后。PD-1-PD-L1疗法可能通过直接作用于GC中的巨噬细胞发挥作用。
Background Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. Although recent studies indicate that PD-1 is also expressed on other immune cells besides T cells, its role remains unclear. This study aims to evaluate PD-1 expression on macrophages and examine its effect on anti-tumor immunity in gastric cancer (GC) patients. Methods The frequency of PD-1(+) macrophages obtained from GC tissue was determined by multicolor flow cytometry (n = 15). Double immunohistochemistry staining of PD-1 and CD68 was also performed to evaluate the correlations among the frequency of PD-1(+) macrophages, clinicopathological characteristics, and prognosis in GC patients (n = 102). Results The frequency of PD-1(+) macrophages was significantly higher in GC tissue than in non-tumor gastric tissue. The phagocytotic activity of PD-1(+) macrophages was severely impaired compared with that of PD-1(-) macrophages. The 5-year disease-specific survival rates in patients with PD-1(+) macrophage(Low) (the frequency of PD-1(+) macrophages; < 0.85%) and those with PD-1(+) macrophage(High) (the frequency of PD-1(+) macrophages; >= 0.85%) were 85.9 and 65.8%, respectively (P = 0.008). Finally, multivariate analysis showed the frequency of PD-1(+) macrophage to be an independent prognostic factor. Conclusions The function of PD-1(+) macrophage was severely impaired and increased frequency of PD-1(+) macrophage worsened the prognosis of GC patients. PD-1-PD-L1 therapies may function through a direct effect on macrophages in GC.