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

Abstract

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.