首页> 美国卫生研究院文献>other >Recovery from Cyclophosphamide-Induced Lymphopenia Results in Expansion of Immature Dendritic Cells Which Can Mediate Enhanced Prime-Boost Vaccination Antitumor Responses In Vivo When Stimulated with the TLR3 Agonist Poly(I:C)
【2h】

Recovery from Cyclophosphamide-Induced Lymphopenia Results in Expansion of Immature Dendritic Cells Which Can Mediate Enhanced Prime-Boost Vaccination Antitumor Responses In Vivo When Stimulated with the TLR3 Agonist Poly(I:C)

机译:从环磷酰胺诱导的淋巴细胞减少中恢复导致未成熟树突状细胞的扩增当用TLR3激动剂Poly(I:C)刺激时该树突状细胞可以介导增强的初免-加强疫苗接种抗肿瘤反应。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Recent preclinical studies suggest that vaccination following adoptive transfer of CD8+ T cells into a lymphopenic host can augment the therapeutic antitumor responses of the transferred cells. However, the mechanism by which the lymphopenic microenvironment benefits Ag-specific CD8+ T cell responses remains elusive. We show herein that induction of lymphodepletion by a single 4 mg cyclophosphamide (CTX) treatment induces a marked expansion of immature dendritic cells (DCs) in the peripheral blood on days 8–16 post-CTX (termed restoration phase). In vitro, these DCs were functional, because they showed normal phagocytosis and effective Ag presentation capability upon activation. In vivo, administration of the TLR3 agonist poly(I:C) at the peak of DC expansion (day 12 postlymphopenia) induced inflammatory cytokine production and increases in the number of activated DCs in lymph nodes. Importantly, boosting with gp10025–33 melanoma peptide combined with poly(I:C) 12 days after an initial priming with the same regimen significantly increased the expansion and the antitumor efficacy of adoptively transferred pmel-1 CD8+ T cells. These responses were abrogated after depletion of activated DCs during Ag boosting. In conclusion, our data show that CTX treatment induces, during the restoration phase, expansion of immature DCs, which are functional and can be exploited in vivo to foster more effective antitumor adoptive immunotherapy strategies.
机译:最近的临床前研究表明,CD8 + T细胞过继转移至淋巴细胞减少宿主后接种疫苗可以增强转移细胞的治疗性抗肿瘤反应。然而,淋巴细胞减少的微环境有益于Ag特异性CD8 + T细胞应答的机制仍然不清楚。我们在此显示,通过单次4 mg环磷酰胺(CTX)处理诱导的淋巴衰竭在CTX后8-16天(称为恢复期)可诱导外周血中未成熟树突状细胞(DC)的显着扩增。在体外,这些DC具有功能,因为它们在激活后显示正常吞噬作用和有效的Ag呈递能力。在体内,在DC扩张高峰期(淋巴细胞减少后第12天)施用TLR3激动剂poly(I:C)会引起炎症细胞因子的产生,并增加淋巴结中激活的DC的数量。重要的是,以相同的方案在初次启动后12天,用gp10025–33黑色素瘤肽与poly(I:C)联合加强免疫可显着提高过继转移的pmel-1 CD8 + 的扩增和抗肿瘤功效。 T细胞。 Ag强化过程中​​激活的DC耗尽后,这些反应就消失了。总之,我们的数据表明,CTX治疗在恢复阶段可诱导未成熟DC的扩增,这些DC具有功能,可在体内用于培养更有效的抗肿瘤过继免疫疗法。

著录项

相似文献

  • 外文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号