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

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.