Division of Surgical Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Clin Cancer Res. 2011 Aug 1;17(15):4987-95. doi: 10.1158/1078-0432.CCR-11-0207. Epub 2011 Jun 20.
We investigated the antitumor reactivity of adoptively transferred effector B cells and the mechanisms by which they may mediate tumor regression in a spontaneous metastases model.
4T1 breast cancer cells were inoculated into the flanks of syngeneic Balb/C mice to prime draining lymph nodes. Tumor-draining lymph nodes (TDLN) were harvested and B cells activated ex vivo with lipopolysaccharide and anti-CD40 monoclonal antibody. These activated B cells were adoptively transferred into mice inoculated with 4T1 tumor in the mammary fat pad. The induction of host T-cell immunity was evaluated.
Activated 4T1 TDLN B cells secreted immunoglobulin G (IgG) in response to tumor cells which was immunologically specific. These activated B cells were capable of mediating specific lysis of tumor cells in vitro. Transfer of these activated B cells alone mediated the inhibition of spontaneous metastases to the lung. Examination of the host revealed that the transfer of these B cells resulted in the induction of tumor-specific T-cell immunity as measured by cytotoxicity and cytokine (IFNγ and granulocyte-macrophage colony-stimulating factor) production. The combined transfer of activated T and B cells from TDLN resulted in tumor regression, which was greater than either cell population alone, with host B cells capable of producing IgG that mediated lysis of tumor in the presence of complement.
We have found that appropriately primed B cells can mediate tumor regression by itself and confers host T-cell antitumor immunity. Furthermore, effector B cells can serve as a useful adjunct in adoptive T-cell therapy.
我们研究了过继转移效应 B 细胞的抗肿瘤反应，以及它们在自发转移模型中可能介导肿瘤消退的机制。
将 4T1 乳腺癌细胞接种到同基因 Balb/C 小鼠的侧腹以启动引流淋巴结。从肿瘤引流淋巴结（TDLN）中采集 B 细胞，并用脂多糖和抗 CD40 单克隆抗体在体外激活。将这些激活的 B 细胞过继转移到乳腺脂肪垫中接种 4T1 肿瘤的小鼠中。评估宿主 T 细胞免疫的诱导。
激活的 4T1 TDLN B 细胞分泌针对肿瘤细胞的免疫球蛋白 G（IgG），具有免疫特异性。这些激活的 B 细胞能够介导体外肿瘤细胞的特异性溶解。单独转移这些激活的 B 细胞可抑制自发转移至肺部。对宿主的检查表明，这些 B 细胞的转移导致了肿瘤特异性 T 细胞免疫的诱导，这可以通过细胞毒性和细胞因子（IFNγ 和粒细胞-巨噬细胞集落刺激因子）的产生来衡量。从 TDLN 共同转移激活的 T 和 B 细胞导致肿瘤消退，这比任何一种细胞群体单独转移都要好，宿主 B 细胞能够产生 IgG，在补体存在的情况下介导肿瘤的溶解。
我们发现适当致敏的 B 细胞可以单独介导肿瘤消退，并赋予宿主 T 细胞抗肿瘤免疫。此外，效应 B 细胞可以作为过继性 T 细胞治疗的有用辅助手段。
