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

Increased regulatory B cells are involved in immune evasion in patients with gastric cancer
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DOI:
10.1038/s41598-019-49581-4
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发表时间:
2019-09-11
期刊:
影响因子:
4.6
通讯作者:
Fujiwara, Yoshiyuki
Fujiwara, Yoshiyuki
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Murakami, Yuki;Saito, Hiroaki;Fujiwara, Yoshiyuki

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越来越多的证据表明,免疫调节细胞参与肿瘤免疫逃避的建立。然而,调节性B细胞(Bcl-2)在其中的作用仍不清楚。在这里,我们确定了胃癌(GC)患者的免疫逃避中的作用。胃癌患者外周血BMPs的频率显著高于健康对照组(P = 0.0023)。胃癌组织中CD 19(+)CD 24(hi)CD 27(+)B细胞的比例明显高于外周血和正常胃组织。羧基荧光素琥珀酰亚胺酯标记显示,CD 19(+)CD 24(hi)CD 27(+)B细胞可抑制自体CD 4(+)T细胞的增殖。此外,CD 19(+)CD 24(hi)CD 27(+)B细胞抑制CD 4(+)T细胞产生干扰素-γ。白细胞介素10和CD 19双染色免疫组化显示,布雷格(低)和布雷格(高)组的5年总生存率分别为65.4%和13.3%(P < 0.0001)。多因素分析显示,胃癌患者的BMPs频率是胃癌患者独立的预后指标。综上所述,我们的研究结果表明,胃癌组织中存在Bcl 2,并表明它们与胃癌患者的预后显着相关。
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.