Immunosuppressive lymphocytes, such as regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs), play crucial roles in tumor escape. To investigate the roles of Tregs and pDCs in papillary thyroid cancer (PTC) plus multinodular non-toxic goiter (MNG), thyroid tissue and blood samples from 30 patients with PTC plus MNG and 30 MNG alone were analyzed for CD4(+) T cell, CD8(+) T cell, FoxP3(+) Treg, ICOS(+)FoxP3(+) Treg, and pDC numbers by immunohistochemistry (IHC), immunofluorescence, and flow cytometry. Plasma concentration of the cytokines interleukin 10 (IL-10) and transforming growth factor β (TGF-β) were measured by enzyme-linked immunosorbent assay as well. Both in thyroid tissue and peripheral blood, the numbers of Foxp3(+) Treg were significantly higher in patients with PTC plus MNG compared to patients with MNG alone; and as a prognostic marker, ICOS(+)Foxp3(+) Tregs represent a stronger predictor of disease progression than the total numbers of Foxp3(+) Tregs. Furthermore, a positive correlation between pDC and ICOS(+)Foxp3(+) Treg numbers in tissue of patients with PTC plus MNG was observed, suggesting that PTC-derived pDCs may induce the differentiation of naive CD4(+) T cells into ICOS(+)Foxp3(+)Tregs. This may be one of the mechanisms underlying tumor escape in PTC plus MNG patients. Our results suggest that Tregs and pDCs together contribute to the tumor escape in patients with PTC plus MNG.

Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) play important roles in the immune escape of cancer. In this study, we investigated pDCs and pDC-induced inducible costimulator (ICOS)+ Treg populations in peripheral blood from gastric cancer (GC) patients and healthy donors by flow cytometry. The distribution of these cells in carcinoma tissue, peritumor tissue, and normal gastric mucosa was detected by immunohistochemistry. Plasma and tissue concentration of the cytokines such as interleukin-10 and transforming growth factor-β1 were also measured. We found that the numbers of pDCs, Tregs, and ICOS+ Tregs in peripheral blood were increased in GC patients compared with healthy donors. In tissue, Tregs and ICOS+ Tregs were found distributing mainly in carcinoma tissue, whereas pDCs were mainly found in peritumor tissue. Moreover, the Foxp3+ICOS+/Foxp3+ cell ratio in carcinoma and peritumor tissue were higher than that in normal tissue. There were more ICOS+ Tregs in tumor and peritumor tissue of late-stage GC patients. There was a positive correlation between pDCs and ICOS+ Tregs in peripheral blood and peritumor tissue from GC patients. In conclusion, pDCs may play a potential role in recruiting ICOS+ Tregs, and both participate in the immunosuppression microenvironment of GC.

Mitofusin-2 (Mfn2) is a mitochondrial outer membrane protein involved in mitochondrial fusion. Its mutation can cause Charcot-Marie-Tooth disease. Recent studies of Mfn2 in cancer research have not included gastric cancer. We confirmed that Mfn2 expression was lower in tumor tissue than in normal gastric mucosal tissue and that it was negatively correlated with tumor size, indicating an anti-tumor role for Mfn2. In vitro experiments showed that Mfn2 overexpression suppressed gastric cancer cell proliferation and colony formation, weakened the invasion and migratory ability of cancer cells by downregulating MMP-2 and MMP-9, halted the cell cycle and induced apoptosis. Western blotting indicated the likely involvement of P21 and PI3K/Akt signaling. Therefore, Mfn2 is a potential anti-tumor gene and a potential therapeutic target for treating gastric cancer. The progress of gastric cancer may be delayed by controlling Mfn2 expression.

BackgroundAccurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy.MethodsWe enrolled 46 patients in this study. The NLR was divided into two groups: high (>2.5) and low (≤2.5). Univariate analysis on progression-free survival (PFS) and overall survival(OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. We analyzed whether chemotherapy normalized high NLR or not, and evaluated the prognostic significance of normalization on survival.ResultsThe univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 16 and 49 months, respectively, P = 0.012; median OS 21 and 52 months, P = 0.113). PFS and OS were also worse for patients with high NLR than for those with low NLR before surgery (median PFS 12 and 35 months, P = 0.019; median OS 21 and 52 months, P = 0.082). Multivariate analysis showed that both NLR before chemotherapy and surgery were independent prognostic factors of PFS. Neoadjuvant chemotherapy normalized high NLR in 11 of 24 patients, and these 11 patients had better median PFS and OS than the 13 patients who had high NLR both before chemotherapy and before surgery (PFS: 35.0 and 10.0 months, P = 0.003; OS: 60 and 16 months, P = 0.042).ConclusionsNLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy.

Cancer-associated inflammation is a key determinant of disease progression and survival in most cancers. The aim of our study was to assess the predictive value of preoperative inflammatory markers, such as the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio, red cell distribution width (RDW), and mean platelet volume, for survival in breast cancer patients. In total, 608 breast cancer patients operated on between January 2009 and December 2011 were included in this observational study. The association between preoperative inflammatory markers and survival outcomes was analyzed. Patients with high NLR (>2.57) or high RDW (>13.45%) showed a significantly lower overall survival rate than those with lower NLR (≤2.57) or lower RDW (≤13.45%). NLR and RDW, along with node stage and molecular subtypes, were independent prognostic factors. There was a significant survival difference according to NLR in the luminal A and triple-negative subtypes (93.3% versus 99.3%, P=0.001; 68.8% versus 95.1%, P=0.000, respectively). The triple-negative subtype was the only subtype in which higher RDW patients showed significantly poor prognosis (81.3% versus 95.5%, P=0.025). Pre-operation NLR and RDW is a convenient, easily measured prognostic indicator for patients with breast cancer, especially in patients with the triple-negative subtype.