B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice.
B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice.
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DOI：
10.4049/jimmunol.0903009
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Tedder TF
中科院分区：
文献类型：
--
作者：
DiLillo DJ;Yanaba K;Tedder TF
B淋巴细胞对细胞免疫反应有正向和负向调节作用。先前的研究表明，在遗传B细胞缺陷小鼠中，T细胞介导的肿瘤免疫增强，表明治疗性B细胞耗竭可以增强肿瘤免疫。为了验证这一假设并量化B细胞对T细胞介导的抗肿瘤免疫反应的贡献，在同源B16黑色素瘤肿瘤转移之前，使用CD20单抗从野生型成年小鼠中去除成熟B细胞。值得注意的是，B细胞缺失小鼠皮下肿瘤体积和肺转移增加了两倍。效应记忆和分泌IFNγ或tnf α的CD4+和CD8+ T细胞诱导在B细胞缺失的肿瘤小鼠中明显受损。在缺乏B细胞的荷瘤小鼠中，肿瘤ag特异性CD8+ T细胞的增殖也受到损害。因此，在这种体内非淋巴肿瘤模型中，B细胞是T细胞活化和细胞免疫的最佳条件。虽然B细胞可能在肿瘤免疫中没有直接的效应作用，但在缺乏B细胞的情况下，受损的T细胞激活和增强的肿瘤生长反驳了先前通过B细胞耗尽来增强肿瘤免疫的建议。相反，除了树突状细胞外，将肿瘤Ags靶向B细胞可能会优化肿瘤定向疫苗和免疫疗法。
B lymphocytes can both positively and negatively regulate cellular immune responses. Previous studies have demonstrated augmented T cell-mediated tumor immunity in genetically B cell-deficient mice, suggesting that therapeutic B cell depletion would enhance tumor immunity. To test this hypothesis and quantify B cell contributions to T cell-mediated anti-tumor immune responses, mature B cells were depleted from wild type adult mice using CD20 mAb prior to syngeneic B16 melanoma tumor transfers. Remarkably, subcutaneous tumor volume and lung metastasis were increased two-fold in B cell-depleted mice. Effector-memory and IFNγ or TNFα-secreting CD4+ and CD8+ T cell induction was significantly impaired in B cell-depleted mice with tumors. Tumor Ag-specific CD8+ T cell proliferation was also impaired in tumor-bearing mice that lacked B cells. Thus, B cells were required for optimal T cell activation and cellular immunity in this in vivo non-lymphoid tumor model. While B cells may not have direct effector roles in tumor immunity, impaired T cell activation and enhanced tumor growth in the absence of B cells argues against previous proposals to augment tumor immunity through B cell depletion. Rather, targeting tumor Ags to B cells in addition to dendritic cells is likely to optimize tumor-directed vaccines and immunotherapies.
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影响因子：
6.4
作者：
GORDON, J;HOLDEN, HT;FELDMAN, M
通讯作者：
FELDMAN, M
DOI：
10.1038/newbio242148a0
发表时间：
1973-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
FIDLER, IJ
通讯作者：
FIDLER, IJ
影响因子：
4.4
作者：
Hamaguchi, Y;Uchida, J;Tedder, TF
通讯作者：
Tedder, TF
影响因子：
11.2
作者：
Inoue, Satoshi;Leitner, Wolfgang W.;Scott, Dorothy
通讯作者：
Scott, Dorothy
影响因子：
6
作者：
Hasegawa, Minoru;Hamaguchi, Yasuhito;Tedder, Thomas F.
通讯作者：
Tedder, Thomas F.