...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >CTLA-4 blockade increases IFNγ-producing CD4~+ICOS~(hi) cells to shift the ratio of effector to regulatory T cells in cancer patients
【24h】

CTLA-4 blockade increases IFNγ-producing CD4~+ICOS~(hi) cells to shift the ratio of effector to regulatory T cells in cancer patients

机译：CTLA-4阻滞增加癌症患者中产生IFNγ的CD4〜+ ICOS〜（hi）细胞的转移，从而改变效应子与调节性T细胞的比例

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Significant anti-tumor responses have been reported in a small subset of cancer patients treated with the immunotherapeutic agent anti-CTLA-4 antibody. All clinical trials to date, comprising over 3,000 patients, have been conducted in the metastatic disease setting, which allows for correlation of drug administration with clinical outcome but has limited analyses of intermediate biomarkers to indicate whether the drug has impacted human immune responses within the tumor microenvironment. We conducted a pre-surgical clinical trial in six patients with localized bladder cancer, which allowed for correlation of drug administration with biomarkers in both blood and tumor tissues but did not permit correlation with clinical outcome. We found that CD4 T cells from peripheral blood and tumor tissues of all treated patients had markedly increased expression of inducible costimulator (ICOS). These CD4~+ICOS~(hi) T cells produced IFN-gamma (IFNγ) and could recognize the tumor antigen NY-ESO-1. Increase in CD4~+ICOS~(hi) cells led to an increase in the ratio of effector to regulatory T cells. To our knowledge, these are the first immunologic changes reported in both tumor tissues and peripheral blood as a result of treatment with anti-CTLA-4 antibody, and they may be used to guide dosing and scheduling of this agent to improve clinical responses.
机译：在用免疫治疗剂抗CTLA-4抗体治疗的一小部分癌症患者中，已报告了重要的抗肿瘤反应。迄今为止，已在转移性疾病环境中进行了包括3,000多名患者在内的所有临床试验，该试验可将药物给药与临床结果相关联，但对中间生物标志物的分析有限，以表明该药物是否已影响肿瘤内的人类免疫应答微环境。我们对六名局限性膀胱癌患者进行了术前临床试验，该试验允许药物给药与血液和肿瘤组织中的生物标志物相关，但与临床结果无关。我们发现，所有接受治疗的患者的外周血和肿瘤组织中的CD4 T细胞的表达均显着增加。这些CD4 ++ ICOS_（hi）T细胞产生IFN-γ（IFNγ），并且可以识别肿瘤抗原NY-ESO-1。 CD4 ++ ICOS_（hi）细胞的增加导致效应子与调节性T细胞的比率增加。据我们所知，这些是抗CTLA-4抗体治疗后在肿瘤组织和外周血中首次报道的免疫学变化，它们可用于指导该药物的给药和时间表以改善临床反应。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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