Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
Department of Surgery, Japanese Red Cross Tottori Hospital, 117 Shotoku-cho, Tottori, 680-8517, Japan.
BMC Cancer. 2020 Mar 4;20(1):175. doi: 10.1186/s12885-020-6629-6.
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.
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).
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 (the frequency of PD-1 macrophages; < 0.85%) and those with PD-1 macrophage (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.
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.
程序性细胞死亡蛋白 1（PD-1）是一种负向调节 T 细胞功能的免疫检查点分子。尽管最近的研究表明 PD-1 也在 T 细胞以外的其他免疫细胞上表达，但它的作用仍不清楚。本研究旨在评估 PD-1 在巨噬细胞上的表达，并研究其对胃癌（GC）患者抗肿瘤免疫的影响。
通过多色流式细胞术（n = 15）测定从 GC 组织中获得的 PD-1 巨噬细胞的频率。还进行了 PD-1 和 CD68 的双重免疫组织化学染色，以评估 PD-1 巨噬细胞的频率与 GC 患者的临床病理特征和预后之间的相关性（n = 102）。
GC 组织中 PD-1 巨噬细胞的频率明显高于非肿瘤性胃组织。与 PD-1 巨噬细胞相比，PD-1 巨噬细胞的吞噬活性严重受损。PD-1 巨噬细胞（PD-1 巨噬细胞频率；< 0.85%）和 PD-1 巨噬细胞（PD-1 巨噬细胞频率；≥ 0.85%）患者的 5 年疾病特异性生存率分别为 85.9%和 65.8%（P = 0.008）。最后，多变量分析显示 PD-1 巨噬细胞频率是独立的预后因素。
PD-1 巨噬细胞的功能严重受损，PD-1 巨噬细胞频率的增加恶化了 GC 患者的预后。PD-1-PD-L1 治疗可能通过直接作用于 GC 中的巨噬细胞发挥作用。
