The role of IL‐10 in malignant pleural effusion (MPE) remains unknown. By using murine MPE models, we observed that an increase in pleural IL‐10 was a significant predictor of increased risk of death. We noted that TH1‐ and TH17‐cell content in MPE was higher in IL‐10–/– mice than in WT mice, and IL‐10 deficiency promoted differentiation into TH1 but not into TH17 cells. A higher fraction of TH1 and TH17 cells in the MPE of IL‐10–/– mice expressed CXCR3 compared with WT mice. We also demonstrated that Lewis lung cancer and colon adenocarcinoma cells secreted large amounts of CXCL10, a ligand of CXCR3, which induced the migration of TH1 and TH17 cells into the MPE, and IFN‐γ could promote this signaling cascade. Furthermore, intrapleural injection of mice with CXCL10‐deficient tumor cells led to decreased TH1‐ and TH17‐cell content in MPE, increased MPE volume, and reduced survival of MPE‐bearing mice. Taken together, we demonstrated that IL‐10 deficiency promoted T‐cell differentiation into TH1 cells and upregulated the CXCR3‐CXCL10 signaling pathway that recruits TH1 and TH17 cells into MPE, ultimately resulting in decreased MPE formation and longer survival time of mice‐bearing MPE.

Inflammatory signaling networks between tumor cells and immune cells contribute to the development of malignant pleural effusion (MPE). B cells have been found in MPE; however, little is known about their roles there. In the present study, by using mouse MPE models, we noted that although the total B cells in MPE were decreased as compared with the corresponding blood and spleen, the percentage of activated naïve B cells expressing higher levels of CD80, CD86, myosin heavy chain-II, CD44, CD69, and programmed cell death-ligand 1 (PD-L1) molecules were increased in wild-type mouse MPE. Compared with wild-type mice, decreased T helper (T)1 cells and increased T17 cells were present in B cell-deficient mouse MPE, which paralleled to the reduced MPE volume and longer survival time. Adoptive transfer of activated naïve B cells into B cell-deficient mice was able to increase T1 cells and decrease T17 cells in MPE and shorten the survival of mice bearing MPE. Furthermore, we demonstrated that activated naïve B cells inhibited T17-cell expansion via the PD-1/PD-L1 pathway and promoted naïve CD4 T-cell differentiation into T1/T17 cells through secreting IL-27/IL-6 independent of the PD-1/PD-L1 pathway. Collectively, our data uncovered a mechanism by which naïve B cells promote MPE formation by regulating T1/T17 cell responses, making these B cells an attractive target for therapeutic intervention in the fight against cancer.

Background:Tumor necrosis factor-alpha (TNF-α) is involved in cancer pathogenesis, and TNF-α-308G>A, a single-nucleotide polymorphism, is associated with cancer prognosis; however, different studies have reported inconsistent results. This meta-analysis aimed to determine the correlation between TNF-α-308G>A polymorphism and the survival of cancer patients.Methods:PubMed, Web of Science, Embase, Wanfang database, VIP database, and China National Knowledge Infrastructure database were used to obtain articles on association between TNF-α-308G>A polymorphism and cancer survival, published until April 2018. A meta-analysis was carried out using Stata 12.0 software to determine the pooled hazard ratio (HR) and 95% confidence intervals (95% CI). Furthermore, publication bias was assessed, and sensitivity analysis was performed to validate the analysis.Results:In total, 13 retrospective cohort studies including 2559 cancer patients were reviewed to estimate the association between TNF-α-308G>A polymorphism and overall survival (OS) of cancer patients. The pooled results suggested that within TNF-α-308G>A polymorphism, genotypes GA+AA/GG (HR = 1.39, 95% CI: 0.90–2.14, P < .001, I2 = 78.1%), GA/GG (HR = 1.06, 95% CI: 0.83–1.36, P = .072, I2 = 53.5%), and AA/AG+GG (HR = 3.28, 95% CI: 0.92–11.72, P = .001, I2 = 85.9%) were not associated with the OS of cancer patients. However, interestingly, the HR was greater for patients with the AA genotype than for those with the GG genotype, suggesting an association between TNF-α-308G>A polymorphism and OS among cancer patients (AA/GG, HR = 2.16, 95% CI: 1.36–3.43, P = .281, I2 = 21.5%).Conclusion:TNF-α-308G>A polymorphism affects the OS of cancer patients and is a potential therapeutic target for cancer.