Abstract
BackgroundProgrammed 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.MethodsThe 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).ResultsThe 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+ macrophageLow (the frequency of PD-1+ macrophages; < 0.85%) and those with PD-1+ macrophageHigh (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.ConclusionsThe 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.
Highlights
Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells
Flow cytometry analysis revealed that PD-1+ macrophages in gastric cancer (GC) tissue express more CD206, indicating that they showed an M2-like profile (Fig. 3)
Since a previous study demonstrated that the phagocytotic ability of PD-1+ macrophages was impaired in colorectal cancer [8], we determined the phagocytotic ability of both PD-1+ and PD-1− macrophages obtained from GC tissue using Zymosan A
Summary
Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. The recent successes of immune checkpoint inhibitors in the treatment of various tumor types clearly indicate that immunotherapy is effective even in patients with cancer. The antibody against programmed cell death 1 (PD-1) is the most clinically successful immune checkpoint drug in the treatment for cancer patients [1,2,3]. Since PD-1 is closely associated with dysfunction of CD4+ and CD8+ T cells, the efficacy of the antibody against PD-1 is widely thought to be attributed to Macrophages are immune cells belong to the innate immune system. They phagocytose bacteria and other harmful organisms and initiate inflammation by releasing pro- inflammatory mediators. Gordon et al recently demonstrated that the function of tumor-associated macrophages (TAMs) that express PD-1 was impaired, Kono et al BMC Cancer (2020) 20:175 which resulted in the progression of tumors [8], indicating that PD-1 was involved in the function of macrophages
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