In vivo sensitized and in vitro activated B cells mediate tumor regression in cancer adoptive immunotherapy.
In vivo sensitized and in vitro activated B cells mediate tumor regression in cancer adoptive immunotherapy.
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DOI：
10.4049/jimmunol.0803773
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发表时间：
2009-09-01
期刊：
影响因子：
--
通讯作者：
Chang AE
中科院分区：
文献类型：
--
作者：
Li Q;Teitz-Tennenbaum S;Donald EJ;Li M;Chang AE
利用肿瘤反应性T细胞的连续性细胞免疫疗法已被证明是一种有前途的癌症治疗策略。然而，我们假设成功的治疗策略不仅要适当刺激细胞免疫，还要刺激体液免疫。我们以前报道过肿瘤引流淋巴结（TDLN）中的B细胞可能具有抗原提呈细胞的功能。在这项研究中，我们确定了TDLN B细胞作为过继免疫治疗模型中的效应细胞。在过继转移到两种组织学上不同的鼠肺转移性肿瘤模型中后，体内致敏和体外活化的TDLN B细胞单独介导有效的（p<0.05）肿瘤消退。先前用化疗或全身照射对宿主进行淋巴细胞清除增强了过继转移的TDLN B细胞在治疗皮下肿瘤以及转移性肺肿瘤中的疗效。此外，与单独的B细胞或T细胞相比，B细胞加T细胞转移导致显著更有效的抗肿瘤应答（p<0.05）。活化的TDLN B细胞对肿瘤产生强烈的体液反应。这通过IgM、IgG和IgG2b的产生是明显的，IgM、IgG和IgG2b特异性结合肿瘤细胞并在补体存在下导致特异性肿瘤细胞裂解。总的来说，这些数据表明，体内致敏和体外活化的B细胞可用作癌症治疗的效应细胞。共转移的活化的B效应细胞和T效应细胞的协同抗肿瘤功效代表了癌症过继免疫治疗的新方法。
Adoptive cellular immunotherapy utilizing tumor-reactive T cells has proven to be a promising strategy for cancer treatment. However, we hypothesize that successful treatment strategies will have to appropriately stimulate not only cellular immunity, but also humoral immunity. We previously reported that B cells in tumor-draining lymph nodes (TDLN) may function as antigen-presenting cells. In this study, we identified TDLN B cells as effector cells in an adoptive immunotherapy model. In vivo primed and in vitro activated TDLN B cells alone mediated effective (p<0.05) tumor regression after adoptive transfer into two histologically distinct murine pulmonary metastatic tumor models. Prior lymphodepletion of the host with either chemotherapy or whole-body irradiation augmented the therapeutic efficacy of the adoptively transferred TDLN B cells in the treatment of subcutaneous tumors as well as metastatic pulmonary tumors. Furthermore, B cell plus T cell transfers resulted in substantially more efficient antitumor responses than B cells or T cells alone (p<0.05). Activated TDLN B cells conferred strong humoral responses to tumor. This was evident by the production of IgM, IgG and IgG2b, which bound specifically to tumor cells and led to specific tumor cell lysis in the presence of complement. Collectively, these data indicate that in vivo primed and in vitro activated B cells can be employed as effector cells for cancer therapy. The synergistic antitumor efficacy of co-transferred activated B effector cells and T effector cells represents a novel approach for cancer adoptive immunotherapy.
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通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
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：
20.3
作者：
Coughlin, CM;Vance, BA;Vonderheide, RH
通讯作者：
Vonderheide, RH
影响因子：
11.2
作者：
Chung, Yeonseok;Kim, Byung-Seok;Kang, Chang-Yuil
通讯作者：
Kang, Chang-Yuil
影响因子：
3.9
作者：
Ito, F;Carr, A;Li, Q
通讯作者：
Li, Q