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.

Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis

“…Concerning GC, the influence of immune checkpoints on the prognosis is broad and complicated [ 25 ]. A previous study conducted by Kono et al argued that the increased frequency of PD-1 positive macrophages might lead to a worse prognosis for GC patients [ 26 ]. Meanwhile, another cohort study from Egg et al reported an elevated cancer risk in patients with CTLA-4 dysfunction [ 27 ].…”

Identification of ALDH3A2 as novel prognostic biomarker in gastric adenocarcinoma by integrated bioinformatics analysis

“…On the aspect of GC, the influence of immune checkpoints on the prognosis is still immense and complicated, as expected [35]. The previous study conducted by Kono et al argued that, the increased frequency of PD-1 positive macrophage may lead to the worse prognosis of GC patients [36]. Meanwhile, another cohort study from Egg et al found elevated cancer risk in patients with CTLA-4 dysfunction [37].…”

Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis

“…Concerning GC, the in uence of immune checkpoints on the prognosis is broad and complicated [25]. A previous study conducted by Kono et al argued that the increased frequency of PD-1 positive macrophages might lead to a worse prognosis for GC patients [26]. Meanwhile, another cohort study from Egg et al reported an elevated cancer risk in patients with CTLA-4 dysfunction [27].…”