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Wei X.,Liaocheng Peoples Hospital | Jin Y.,Reproductive Center | Tian Y.,Hospice | Zhang H.,Liaocheng Peoples Hospital | And 3 more authors.
Tumor Biology | Year: 2015

Multiple factors in the tumor microenvironment were found to inhibit antitumor adaptive immune responses, allowing tumor persistence and growth. In this study, ascites from ovarian cancer patients were collected. We observed that a population of interleukin-10+ B (IL-10+ B) cells was preferentially enriched in the ascites. This population was associated with naive B cell phenotype or IgM or class-switched memory B cell phenotypes. The frequencies of IL-10+ B cells were negatively correlated with the frequencies of interferon gamma-producing (IFN-g+) CD8+ T cells and were positively correlated with the frequencies of Foxp3+ CD4+ T cells. To examine whether increased IL-10+ B cells in ascites could directly result in increased suppression of IFN-g production by CD8+ T cells, we cocultured CD8+ T cells with autologous blood B cells or ascitic B cells and found that CD8+ T cells cocultured with ascitic B cells demonstrated significantly suppressed IFN-g production. This suppression was in part mediated by IL-10 as well as low CD80/CD86 expression, since depletion of IL-10 and stimulation of CD28 partially reverted IL-10+ B cell-mediated suppression. Together, these data demonstrated an additional regulatory mechanism in the tumor microenvironment, which utilizes IL-10+ B cells. © 2015 International Society of Oncology and BioMarkers (ISOBM)

Bu M.,The Maternal and Child Health Hospital of Jinan City | Shen Y.,General Hospital of Shenyang Military Command | An S.,The Maternal and Child Health Hospital of Jinan City | Qi R.,The Maternal and Child Health Hospital of Jinan City | Cai Y.,Jian Guo
Tumor Biology | Year: 2015

Ovarian carcinoma is one of the most severe cancers in women, with a high relapse rate and limited secondary treatment options. To assist research in novel treatment technologies, including CD8+ T cell-base immunotherapy, we examined the effect of tumor-infiltrating regulatory T cells (Tregs) in inhibiting CD8+ T cell inflammation. We found that compared to their peripheral blood counterparts, tumor-infiltrating Tregs exhibited more potent inhibitory function, which was associated with higher interleukin 10 (IL-10) production in tumor-infiltrating Tregs. Blockade of T cell immunoglobulin mucin 3 (TIM3), a regulatory molecule overrepresented on tumor-infiltrating Tregs, had significantly reverted Treg-mediated suppression. Moreover, expression of TIM3 on tumor-infiltrating Tregs was directly correlated with tumor size. Together, our results demonstrated that ovarian tumor-infiltrating Treg cells were more immunosuppressive than their peripheral blood counterparts in a TIM3-dependent fashion. © 2015 International Society of Oncology and BioMarkers (ISOBM)

Jin H.,The Maternal and Child Health Hospital of Jinan City | Wu J.,The Maternal and Child Health Hospital of Jinan City | Yang Q.,Jian Guo | Cai Y.,The Maternal and Child Health Hospital of Jinan City | And 2 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2015

Purpose: Inflammation in chorionic villi is involved in the development of recurrent pregnancy loss (RPL). High mobility group box 1 protein (HMGB1) plays critical roles in inflammation and expression of the protein can be found in chorionic villi. The purpose of the study was to investigate the association between HMGB1 genetic polymorphisms and susceptibility to RPL and to examine the mechanism underlying this correlation. Methods: Two HMGB1 polymorphisms, rs2249825C/G and rs1412125T/C, were examined in 112 RPL patients and 118 healthy controls by the polymerase chain reaction–restriction fragment length polymorphism assay. Results: Percentage of rs2249825GG was significantly increased in patients than in controls (Odd ratio [OR] =2.33, 95 % confidence interval [CI]: 1.18–4.58, P = 0.013). Also, prevalence of rs2249825G allele was significantly higher in RPL cases (OR = 1.77, 95 % CI: 1.20–2.62, P = 0.004). Function analysis of rs2249825C/G revealed that the polymorphism did not affect serum level of HMGB1. Interestingly, we found significantly increased level of HMGB1 in chorionic villi from RPL patients. Moreover, patients with rs2249825GG genotype presented significantly elevated level of HMGB1 in chorionic villi compared to those with CG or CC genotypes. Conclusions: These results suggest that HMGB1 rs2249825C/G polymorphism is associated with increased risk of RPL and can elevate gene expression in chorionic villi. © 2015, Springer Science+Business Media New York.

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