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衰老相关的 B7-DC+ B 细胞通过 Th1 和 Th17 诱导增强抗肿瘤免疫。

Aging-associated B7-DC+ B cells enhance anti-tumor immunity via Th1 and Th17 induction.

机构信息

Cancer Therapy and Research Center, San Antonio, TX 78229, USA.

出版信息

Aging Cell. 2012 Feb;11(1):128-38. doi: 10.1111/j.1474-9726.2011.00764.x. Epub 2011 Nov 28.

Abstract

Because most patients with cancer are aged and because immunological functions are altered during aging, it is important to account for aging-associated immunological alterations in the design of new cancer immunotherapies. We thus compared immune populations in young and aged mice and found that B7-DC(+) (PD-L2/CD273) B cells, a minor population in young mice, were significantly increased in aged mice. Induction of both Th1 and Th17 cells was significantly augmented by B7-DC(+) B cells from aged mice, and this effect was blocked with anti-B7-DC antibodies in vitro and in vivo. Moreover, retardation of tumor growth in aged mice was largely B7-DC dependent. Tumor growth in young mice was significantly inhibited by immunization with B7-DC(+) B cells from aged mice owing to increased induction of tumor antigen-specific cytotoxic T lymphocytes. These data indicate that B7-DC(+) B cells could play an important role in aging-associated cancer immunopathology as well as in other aging-associated diseases and further suggest that B7-DC(+) B cells have potential for future cancer immunotherapy.

摘要

由于大多数癌症患者年龄较大,并且免疫功能在衰老过程中发生改变,因此在设计新的癌症免疫疗法时,必须考虑与衰老相关的免疫改变。因此,我们比较了年轻和老年小鼠中的免疫群体,发现 B7-DC(+)(PD-L2/CD273)B 细胞在年轻小鼠中是一个小群体,而在老年小鼠中显著增加。B7-DC(+)B 细胞从老年小鼠中显著增强了 Th1 和 Th17 细胞的诱导,并且这种作用可以通过体外和体内的抗 B7-DC 抗体来阻断。此外,B7-DC 的延迟肿瘤生长在老年小鼠中是主要依赖的。由于诱导了肿瘤抗原特异性细胞毒性 T 淋巴细胞的增加,用来自老年小鼠的 B7-DC(+)B 细胞免疫接种可显著抑制年轻小鼠的肿瘤生长。这些数据表明,B7-DC(+)B 细胞可能在与衰老相关的癌症免疫病理学以及其他与衰老相关的疾病中发挥重要作用,并进一步表明 B7-DC(+)B 细胞具有用于未来癌症免疫治疗的潜力。

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