Autoimmune thyroiditis as an indicator of autoimmune sequelae during cancer immunotherapy.
Autoimmune thyroiditis as an indicator of autoimmune sequelae during cancer immunotherapy.
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自身免疫性甲状腺炎作为癌症免疫治疗期间自身免疫后遗症的指标。
DOI：
10.1016/j.autrev.2009.02.034
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发表时间：
2009
影响因子：
13.6
通讯作者：
Wei,Wei-Zen
中科院分区：
文献类型：
--
作者：
Kong,Yi-chiM;Jacob,JenniferB;Flynn,JeffreyC;Elliott,BruceE;Wei,Wei-Zen
通过靶向T细胞网络改善癌症免疫疗法也会引发自身免疫。我们破坏了调节性T细胞（Treg）功能，以探测乳腺癌疫苗接种和自身免疫性甲状腺炎（EAT）之间的平衡，在四种模型中，特别注意MHC相关的易感性，EAT诱导与小鼠甲状腺球蛋白（mTg）无佐剂，和耐受Her-2/neu转基因小鼠。1)在EAT抗性BALB/c小鼠中，Treg耗竭增强肿瘤消退，并促进轻度甲状腺炎诱导。2)在表达HLA-DR 3（EAT易感等位基因）的Her-2耐受性C57 BL/6小鼠中，Her-2 DNA疫苗接种必须遵循Treg耗竭（Her-2xDR 3）F1小鼠以抵抗肿瘤攻击;甲状腺炎发病率受EAT抗性IAb等位基因的调节。3)在neu耐受、EAT耐受的BALB/c小鼠中，植入的neu+肿瘤也仅在Treg耗竭和DNA疫苗接种后消退。肿瘤免疫是长期的，提供保护，防止自发性肿瘤发生。在这三种情况下，来自同时发生的肿瘤消退和EAT发展的免疫刺激具有明显的相互增强作用。4)在Treg耗尽的EAT易感CBA/J小鼠中，通过用细胞疫苗免疫建立了强的肿瘤保护。mTg注射导致甲状腺炎发病率和严重程度增加。具有MHC II类多样性的组合模型应有助于自身免疫风险评估和管理，同时产生肿瘤免疫。
Improving cancer immunotherapy by targeting T cell network also triggers autoimmunity. We disrupted regulatory T cell (Treg) function to probe the balance between breast cancer vaccination and autoimmune thyroiditis (EAT) in four models, with particular attention to MHC-associated susceptibility, EAT induction with mouse thyroglobulin (mTg) without adjuvant, and tolerance to Her-2/neu in transgenic mice. 1) In EAT-resistant BALB/c mice, Treg depletion enhanced tumor regression, and facilitated mild thyroiditis induction. 2) In Her-2 tolerant C57BL/6 mice expressing HLA-DR3, an EAT-susceptibility allele, Her-2 DNA vaccinations must follow Treg depletion for (Her-2xDR3)F1mice to resist tumor challenge; thyroiditis incidence was moderated by the EAT-resistant IAballele. 3) In neu tolerant, EAT-resistant BALB/c mice, implanted neu+tumor also regressed only after Treg depletion and DNA vaccinations. Tumor immunity was long-term, providing protection from spontaneous tumorigenesis. In all three, immune stimuli from concurrent tumor regression and EAT development have a noticeable, mutually augmenting effect. 4) In Treg-depleted, EAT-susceptible CBA/J mice, strong tumor protection was established by immunization with a cell vaccine. mTg injections led to greater thyroiditis incidence and severity. Combination models with MHC class II diversity should facilitate autoimmunity risk assessment and management while generating tumor immunity.