胃癌组织中 PD-1 阳性巨噬细胞的增加与胃癌患者的不良预后密切相关。

Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients.

机构信息

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.

出版信息

BMC Cancer. 2020 Mar 4;20(1):175. doi: 10.1186/s12885-020-6629-6.

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 (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.

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.

背景

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。

方法

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）。

结果

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。