期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 39, 页码 14987-14992出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0806075105
关键词
-
资金
- Physician-Scientist Program
- Institutional Research Grant from the University of Texas
- Anderson Cancer Center
- American Society of Clinical Oncology
- Bristol-Myers Squibb
Significant anti-tumor responses have been reported in a small subset of cancer patients treated with the immunotherapeutic agent antiCTLA-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(+) ICOShi T cells produced IFN-gamma (IFN gamma) and could recognize the tumor antigen NY-ESO-1. Increase in CD4(+) ICOShi 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据