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Increased regulatory B cells are involved in immune evasion in patients with gastric cancer

Year: 2020
Type: dissertation
Study design: Observational Study
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 + CD24 hi CD27 + B cells in GC tissue was significantly higher than in peripheral blood and healthy gastric tissue.Carboxyfluorescein succinimidyl ester labeling revealed that CD19 + CD24 hi CD27 + B cells could suppress the proliferation of autologous CD4 + t cells.Moreover, CD19 + CD24 hi CD27 + 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 Breg Low and Breg High 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.Gastric cancer (GC) is one of the most common malignancies and ranks second among all cancer-related deaths worldwide 1 .Recently, it was shown that the antibody to programmed cell death protein 1, known as the immune checkpoint inhibitor, is effective in the treatment of unresectable advanced and recurrent GC 2 .This clearly indicates that effective immunity to GC cells can be induced in GC patients, which improves their prognosis.The expression of tumor rejection antigens such as MAGE 1-3 and the presence of tumor-specific cytotoxic T cells have been reported in GC patients 3,4 , but the spontaneous rejection of established GC is rarely seen.Furthermore, the efficacy of immune checkpoint inhibitors is still limited 2 , possibly because of tumoral immune evasion.Some mechanisms responsible for tumoral immune evasion in GC patients include the production of immune suppressive cytokines, such as interleukin (IL)-10 and transforming growth factor-beta 1, by tumor cells and other cells exist at the tumor microenviroment 5,6 , and the impaired function of immune cells including CD8+ T cells and natural killer cells 7 .The presence of immune regulatory cells is also important in tumoral immune evasion.One of the most characterized immune regulatory cells are regulatory T cells (Treg), whose levels are increased in both peripheral blood and tumor tissue of GC patients where they are associated with tumoral immune evasion 8 .B lymphocytes play a central role in humoral immunity through the production of immunoglobulin.Recently, a subset of B cells, regulatory B cells (Bregs), was demonstrated to exert immunoregulatory functions through production of the immunosuppressive cytokine IL-10 9 .Although most Breg studies have focused on autoimmune mouse models and patients with autoimmune diseases, several mouse cancer studies have also revealed the existence of protumorigenic Bregs [10][11][12] .At present, however, the subset composition and function of Bregs in human cancer including GC are largely unclear.Therefore, we undertook the present study to evaluate Bregs in GC to assess possible mechanisms for immune evasion by Bregs.
Institution: Tottori University
Language: English
Subfield: Immunology
Open Access status: green
OpenAlex ID: W7146055297
Cites: 19
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Related to: 10