Adoptive transfer of tumor reactive B cells confers host T-cell immunity and tumor regression.
Adoptive transfer of tumor reactive B cells confers host T-cell immunity and tumor regression.
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DOI：
10.1158/1078-0432.ccr-11-0207
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发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Chang AE
中科院分区：
文献类型：
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作者：
Li Q;Lao X;Pan Q;Ning N;Yet J;Xu Y;Li S;Chang AE
我们研究了过继转移效应B细胞的抗肿瘤反应性及其在自发转移模型中介导肿瘤消退的机制。将4 T1乳腺癌细胞接种到同系Balb/C小鼠的侧腹中以引发引流淋巴结。收获肿瘤引流淋巴结（TDLN），用LPS和抗-CD 40 mAb离体活化B细胞。将这些活化的B细胞过继转移到在乳房脂肪垫中接种有4 T1肿瘤的小鼠中。评价宿主T细胞免疫的诱导。活化的4 T1 TDLN B细胞分泌IgG应答肿瘤细胞，这是免疫特异性的。这些活化的B细胞能够介导体外特异性溶解肿瘤细胞。这些活化的B细胞单独转移介导了对自发转移到肺的抑制。对宿主的检查显示，这些B细胞的转移导致诱导肿瘤特异性T细胞免疫，如通过细胞毒性和细胞因子（IFNγ和GM-CSF）产生所测量的。从TDLN联合转移活化的T和B细胞导致肿瘤消退，其大于单独的任一细胞群，其中宿主B细胞能够产生IgG，其在补体存在下介导肿瘤的溶解。我们已经发现，适当地致敏的B细胞本身可以介导肿瘤消退，并赋予宿主T细胞抗肿瘤免疫力。此外，效应B细胞可作为过继性T细胞治疗中的有用辅助物。
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 LPS and anti-CD40 mAb. 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 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 GM-CSF) 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.