An investigation regarding regulatory B cells in gastrointestinal cancer.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10498
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tottori University
• Principal Investigator: SAITO Hiroaki 鳥取大学, 医学部, 准教授 (20335532)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 制御性B細胞 / 腫瘍免疫 / 細胞性免疫 / 胃癌 / 大腸癌 / 免疫逃避機構

Outline of Final Research Achievements

The frequency of peripheral regulatory B cells (Bregs) was significantly higher in gastric cancer (GC) patients than in healthy controls. The frequency of Bregs in GC tissue was significantly higher than in peripheral blood and healthy gastric tissue. We also confirmed that the same phenomenon could be observed in esophageal and colorectal cancer. With regard to the function of Bregs obtained from GC patients, carboxyfluorescein succinimidyl ester labeling revealed that Bregs could suppress the proliferation of autologous CD4+ T cells. Moreover, Bregs 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 patients with BregHigh (13.3%) was significantly lower than that of patients with BregLow (65.4%, P < 0.0001). Multivariate analysis indicated that the frequency of Bregs was an independent prognostic indicator in GC patients.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

本研究により消化器癌患者の腫瘍局所には細胞性免疫抑制機能を有する制御性B細胞が多く存在し、予後を悪化させることが明らかとなった。このことは制御性B細胞が消化器癌に対する新たな免疫治療を開発する重要なターゲットになることを示す結果である。今後の検討により制御性B細胞をターゲットとした治療法が開発されれば、消化器癌患者の予後向上につながると考えられる。