期刊
CLINICAL CANCER RESEARCH
卷 17, 期 12, 页码 4101-4109出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-11-0407
关键词
-
类别
资金
- Pfizer Inc.
- Melanoma Research Foundation
- NIH [2U54 CA119347]
- Fred L. Hartley Family Foundation
- Jonsson Cancer Center Foundation
- Caltech-UCLA Joint Center for Translational Medicine
Background: CTLA4 blocking monoclonal antibodies provide durable clinical benefit in a subset of patients with advanced melanoma mediated by intratumoral lymphocytic infiltrates. A key question is defining whether the intratumoral infiltration (ITI) is a differentiating factor between patients with and without tumor responses. Methods: Paired baseline and postdosing tumor biopsy specimens were prospectively collected from 19 patients with metastatic melanoma, including 3 patients with an objective tumor response, receiving the anti-CTLA4 antibody tremelimumab within a clinical trial with primary endpoint of quantitating CD8(+) cytotoxic T-lymphocyte (CTL) infiltration in tumors. Samples were analyzed for cell density by automated imaging capture and further characterized for functional lymphocyte properties by assessing the cell activation markers HLA-DR and CD45RO, the cell proliferation marker Ki67, and the regulatory T-cell marker FOXP3. Results: There was a highly significant increase in ITI by CD8(+) cells in biopsy samples taken after tremelimumab treatment. This included increases between 1-fold and 100-fold changes in 14 of 18 evaluable cases regardless of clinical tumor response or progression. There was no difference between the absolute number, location, or cell density of infiltrating cells between clinical responders and patients with nonresponding lesions that showed acquired intratumoral infiltrates. There were similar levels of expression of T-cell activation markers (CD45RO, HLA-DR) in both groups and no difference in markers for cell replication (Ki67) or the suppressor cell marker FOXP3. Conclusion: CTLA4 blockade induces frequent increases in ITI by T cells despite which only a minority of patients have objective tumor responses. Clin Cancer Res; 17(12); 4101-9. (C) 2011 AACR.
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