The combination of CRP/Alb ratio and NLR may be useful in predicting prognosis in gastric cancer patients.

No abstract

Accumulating evidence has indicated that immune regulatory cells are involved in the establishment of tumoral immune evasion. However, the role of regulatory B cells (Bregs) in this remains unclear. Here, we identified a role for Bregs in immune evasion in gastric cancer (GC) patients. The frequency of peripheral Bregs was significantly higher in GC patients than in healthy controls (P = 0.0023). Moreover, the frequency of CD19+CD24hiCD27+ B cells in GC tissue was significantly higher than in peripheral blood and healthy gastric tissue. Carboxyfluorescein succinimidyl ester labeling revealed that CD19+CD24hiCD27+ B cells could suppress the proliferation of autologous CD4+ T cells. Moreover, CD19+CD24hiCD27+ B cells inhibited the production of interferon-gamma by CD4+ T cells. Double staining immunohistochemistry of interleukin-10 and CD19 revealed 5-year overall survival rates of 65.4% and 13.3% in BregLow and BregHigh groups, respectively (P < 0.0001). Multivariate analysis indicated that the frequency of Bregs was an independent prognostic indicator in GC patients. Taken together, our results show the existence of Bregs in GC tissue, and indicate that they are significantly correlated with the prognosis of GC patients.

The combination of pre- and postoperative NLRs appears to be useful for predicting the prognosis of gastric cancer patients.

Background/Aim: Although many prognostic indicators have been identified for resectable gastric cancer (GC), prognostic indicators for unresectable GC (urGC) have not been widely studied. The aim of the current study was to investigate prognostic indicators that could be determined through routine blood examinations in patients with urGC. Patients and Methods: We retrospectively analyzed clinicopathological factors in 92 patients with unresectable advanced and recurrent gastric adenocarcinoma. Results: Based on receiver operating curve analysis, neutrophil-to-lymphocyte ratio (NLR) had the highest area under curve for 1-year survival among patients with urGC. Among patients with urGC, NLR was significantly higher in those with advanced disease compared to those with recurrent disease (p=0.0051); and in those with peritoneal metastasis compared to those without peritoneal metastasis (p=0.041). Patients were divided into NLR High (NLR≥2.83) and NLR Low (NLR<2.83). Their median survival times were NLR High : 9.1 months and NLR Low : 17.1 months (p<0.0001). NLR was also inversely correlated with survival period (r=0.496, p<0.0001); and NLR measured one month after starting chemotherapy was significantly associated with the prognosis of both NLR Low and NLR High patients with urGC. Multivariate analysis showed NLR to be an independent predictor of overall survival in these patients. Conclusion: NLR is useful for predicting the prognosis of patients with unresectable GC. An estimated 1,300,000 new cases of gastric cancer (GC)

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.

Tumor-associated macrophages (TAMs) have an alternatively activated macrophage phenotype (M2) and promote cancer cell proliferation, angiogenesis and metastasis. Nuclear factor-kappaB (NF-κB) is one of the master regulators of macrophage polarization. Here, we investigated the effect of inhibition of NF-κB activity by small interfering RNA (siRNA) on the pro-tumor response of macrophages located in the tumor microenvironment in vitro. We used mouse peritoneal macrophages cultured in conditioned medium from colon-26 cancer cells as an in vitro TAM model (M2-like macrophages). Transfection of NF-κB (p50) siRNA into M2-like macrophages resulted in a significant decrease in the secretion of interleukin (IL)-10 (a T helper 2 (Th2) cytokine) and a significant increase of T helper 1 (Th1) cytokine production (IL-12, tumor necrosis factor-α, and IL-6). Furthermore, vascular endothelial growth factor production and matrix metalloproteinase-9 mRNA expression in M2-like macrophages were suppressed by inhibition of NF-κB expression with NF-κB (p50) siRNA. In addition, there was a reduction of arginase mRNA expression and increase in nitric oxide production. The cytokine secretion profiles of macrophages cultured in conditioned medium from either B16BL6 or PAN-02 cancer cells were also converted from M2 to classically activated (M1) macrophages by transfection of NF-κB (p50) siRNA. These results suggest that inhibition of NF-κB activity in M2-like macrophages alters their phenotype toward M1.

The incidence of perioperative DVT was low for patients undergoing gastric cancer surgery. Therefore, the risk-stratified application of perioperative pharmacologic thromboprophylaxis is thought to be more appropriate than routine pharmacologic thromboprophylaxis for Japanese patients undergoing surgery for gastric cancer.