期刊
CLINICAL CANCER RESEARCH
卷 14, 期 18, 页码 5900-5906出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-08-0846
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类别
资金
- Melanoma Research Foundation
- Valvano Foundation for Cancer Research
- NIH [K24 CA93670, P30-CA16058, P01 CA95426-01A1]
Purpose: The precise molecular targets of IFN-alpha therapy in the context of malignant melanoma are unknown but seem to involve signal transducers and activators of transcription 1 signal transduction within host immune effector cells. We hypothesized that the in vitro transcriptional response of patient peripheral blood mononuclear cells (PBMC) to IFN-alpha would be similar to the in vivo response to treatment with high-dose IFN-alpha. Experimental Design: The gene expression profiles of PBMCs and immune cell subsets treated in vitro with IFN-alpha were evaluated, as were PBMCs obtained from melanoma patients receiving adjuvant IFN-alpha. Results: Twenty-seven genes were up-regulated in PBMCs from normal donors after treatment with IFN-alpha in vitro for 18 hours (>2-fold, P < 0.001). A subset of these genes (in addition to others) was significantly expressed in IFN-alpha- treated T cells, natural killer cells, and monocytes. Analysis of gene expression within PBMCs from melanoma patients (n = 13) receiving high-dose IFN-alpha-2b (20 MU/m(2) i.v.) revealed significant up-regulation (>2-fold) of 21 genes (P < 0.001). Also, the gene expression profile of in vitro IFN-alpha- stimulated patient PBMCs was similar to that of PBMCs obtained from the same patient after IFN-alpha therapy. Conclusions: This report is the first to describe the transcriptional response of T cells, natural killer cells, and monocytes to IFN-alpha and characterize the transcriptional profiles of PBMCs from melanoma patients undergoing IFN-alpha immunotherapy. In addition, it was determined that microarray analysis of patient PBMCs after in vitro stimulation with IFN-alpha may be a useful predictor of the in vivo response of immune cells to IFN-alpha immunotherapy.
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