期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 124, 期 5, 页码 2147-2159出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI69611
关键词
-
资金
- Conquer Cancer Foundation of American Society of Clinical Oncology
- National Basic Research Program of China [2010CB529406]
- Department of Transfusion Medicine
- Clinical Center and trans-NIH Center for Human Immunology (CHI)
- NIH
In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-alpha, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-alpha response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-alpha signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-alpha. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.
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