12/16/2023 0 Comments Elucidate aiBy the co-culture system in vitro, we evaluated the contribution of GC cell supernatant to CD4 + T cell dysfunction. We confirmed that serum level of TGF-β1 was elevated in GC and correlated with increased CD4 +Foxp3 + Treg cells. In this study, we examined the serum level of TGF-β1 in gastric cancer patients and analyzed the correlation of TGF-β1 with the prevalence of Tregs. However, the underlying mechanism of TGF-β1 responsible for regulating gastric cancer immunosuppression has not been fully elucidated yet. The mechanism of TGF-β1 function in gastric cancer is believed to be mediated primarily by increasing the deposition of extracellular matrix and immunosuppression. Over the past few years, significant progress has been made in defining the cellular and molecular basis for these protumorigenic effects of TGF-β1 within tumor microenvironment. In contrast, other studies have shown that the development and functional capacity of CD4 +CD25 + Tregs is normal in TGF-β1 deficient mice, questioning a role for TGF-β1 in mediating Treg development and function. ![]() In vitro, studies have shown that TGF-β1 can impose a regulatory phenotype on CD4 +CD25 - T cells through the induction of Foxp3 expression. ![]() Transforming growth factor-β1 (TGF-β1), as well as other mediators such as prostaglandin E2 and H-ferritin, has been reported to induce Treg cells. However, the detailed mechanism underlying the induction of Tregs during GC progress remains undefined. These results strongly suggest that gastric cancer-related factors induce and/or expand the accumulation of Tregs. Interestingly, our and others data showed that after patients received curative resection for GC, the increased proportion of Tregs was significantly restored to normal levels. In addition, we found increased expression of Foxp3 protein per cell in tumor-infiltrating Tregs and Tregs can mediate immune suppression via COX-2 production. Our recent results have showed that the existence of Tregs maintained immune tolerance in gastric tumor microenvironments. Recently, emerging evidence suggests that CD4 + regulatory T cells (Tregs) play an important role in tumor escape from immunological control by suppressing the activation and proliferation of T cells, B cells, and natural killer (NK) cells. ![]() Certain tumors, including GC, have developed the capacity to escape immune surveillance or to inhibit immune functions. Although the incidence of GC is declining in most developed countries, it remains one of the most common causes of cancer-related death in many Asian countries, such as China, Japan, and Korea. Gastric cancer (GC) is a common fatal malignancy from cancer worldwide. Gastric cancer cells upregulated the production of TGF-β1 and blockade of TGF-β1 partly abrogated Tregs phenotype.ĬONCLUSION: Gastric cancer cell can induce Tregs development via producing TGF-β1, by which the existence of cross-talk between the tumor and immune cells might regulate anti-tumor immune responses. Finally, we demonstrated that gastric cancer cells induced the increased CD4 +Foxp3 + Tregs via producing TGF-β1. Moreover, using the purified CD4 +CD25 - T cells, we confirmed that the increased Tregs were mainly induced from the conversation of CD4 +CD25 - naive T cells, and induced Tregs were functional and able to suppress the proliferation of effector T cells. A significant higher frequency of CD4 +Foxp3 + Tregs was observed in PBMCs cultured with the supernatant of MGC than GES-1 (10.6% ± 0.6% vs 8.7% ± 0.7%, P < 0.05). Furthermore, the higher TGF-β1 level correlated with the increased population of CD4 +Foxp3 + Tregs in advanced gastric cancer ( r = 0.576, P < 0.05). RESULTS: The level of serum TGF-β1 in gastric cancer patients (15.1 ± 5.5 ng/mL) was significantly higher than that of the gender- and age-matched healthy controls (10.3 ± 3.4 ng/mL) ( P < 0.05). Neutralizing anti-TGF-β1 antibody was added to the co-culture system for neutralization experiments. The carboxyfluorescein diacetatesuccinimidyl ester (CFSE) dilution assay was performed to evaluate the proliferation characteristics of induced Tregs. The production of TGF-β1 was detected in supernatant of MGC and GES-1. The normal gastric mucosa cell line, GES-1, was used as the control. The gastric cancer microenvironment was modeled by establishing the co-culture of gastric cancer cell line, MGC-803, with sorting CD4 + T cells. ![]() Foxp3 gene expression was analyzed by real-time polymerase chain reaction. METHODS: The frequencies of CD4 +Foxp3 + Tregs and the level of transforming growth factor-β1 (TGF-β1) were analyzed from 56 patients with gastric cancer by flow cytometry and enzyme-linked immunosorbent assay respectively. AIM: To elucidate the molecular and cellular features responsible for the increase of regulatory T cells (Tregs) in gastric cancer.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |