Tissue distribution of target antigen has a decisive influence on the outcome of adoptive cancer immunotherapy
Tissue distribution of target antigen has a decisive influence on the outcome of adoptive cancer immunotherapy
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DOI：
10.1182/blood-2002-04-1032
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发表时间：
2003-01-15
期刊：
影响因子：
20.3
通讯作者：
Perreault, C
中科院分区：
文献类型：
--
作者：
Meunier, MC;Roy-Proulx, G;Perreault, C
同种异体 T 细胞的过继转移对于根除白血病细胞具有无与伦比的功效。因此，我们试图从动力学角度评估 T 细胞和同种异体白血病细胞之间的相互作用。针对模型 B6(dom1) 次要组织相容性抗原引发的 T 细胞被过继转移到受辐射的 B10（B6(dom1) 阳性）和同类 B10.H7(b)（B6(dom1) 阴性）受体中，其中一些受体还注射了 EL4 白血病/淋巴瘤细胞（B6(dom1) 阳性）。一个重要的发现是，目标表位的组织分布极大地影响了过继性癌症免疫治疗的结果。 B10 受体中 B6(dom1) 的广泛表达诱导抗原特异性 T 细胞凋亡和功能障碍。此外，在白血病 B10 和 B.10.H7(b) 宿主中，在骨髓（EL4 细胞生长的主要部位）中检测到效应/记忆 B6(dom1) 特异性 T 细胞的大量积累。受体骨髓中效应/记忆细胞的积累是EL4依赖性的，其动力学与在受体脾脏中观察到的不同。我们的结论是，必须设计策略来防止面临高抗原负载的过继转移 T 细胞凋亡，并且对于肿瘤生长部位的免疫反应的局部监测可能对于对过继免疫疗法的功效进行有意义的评估是强制性的。 (C) 2003 年，美国血液学会。
Adoptive transfer of allogeneic T cells has unmatched efficacy to eradicate leukemic cells. We therefore sought to evaluate in kinetic terms interactions between T cells and allogeneic leukemic cells. T cells primed against the model B6(dom1) minor histocompatibility antigen were adoptively transferred in irradiated B10 (B6(dom1)-positive) and congenic B10.H7(b) (B6(dom1)-negative) recipients, some of which were also injected with EL4 leukemia/lymphoma cells (B6(dom1)-positive). A key finding was that the tissue distribu-tion of the target epitope dramatically influenced the outcome of adoptive cancer immunotherapy. Widespread expression of B6(dom1) in B10 recipients induced apoptosis and dysfunction of antigen-specific T cells. Furthermore, in leukemic B10 and B.10.H7(b) hosts, a massive accumulation of effector/memory B6(dom1)-specific T cells was detected in the bone marrow, the main site of EL4 cell growth. The accumulation of effector/memory cells in recipient bone marrow was EL4 dependent, and its kinetics was different from that observed in recipient spleen. We conclude that strategies must be devised to prevent apoptosis of adoptively transferred T cells confronted with a high antigen load and that local monitoring of the immune response at the site of tumor growth may be mandatory for a meaningful assessment of the efficacy of adoptive immunotherapy. (C) 2003 by The American Society of Hematology.