Evidence of Systemic Th2-Driven Chronic Inflammation in Patients with Metastatic Melanoma

摘要: Purpose: Immunotherapeutic modalities are commonly used for treatment of patients with melanoma. The therapeutic success in preclinical models has not yielded the expected clinical results. To understand this discrepancy, we attempted to define immune homeostasis 209 melanoma across stages disease relative normal controls. Experimental Design: Peripheral blood mononuclear cells (PBMC) and plasma were collected from healthy donors. PBMC analyzed frequencies natural killer, dendritic, T their functional status. Matched samples concentrations 27 cytokines, chemokines, growth factors. RNA was isolated 24 metastatic tumor biopsies profiled by microarray analysis. Results: frequency T, dendritic does significantly change However, Th2 cytokines [interleukin (IL)-4, IL-5, IL-10, IL-13] tumor-bearing higher than those resected Expression array analysis revealed that malignant melanocytes source but did highly up-regulate vascular endothelial factor (VEGF) transcripts, consistent VEGF concentrations. In vitro exposure lead repolarization Th1 emulating state Conclusions: Patients exist a Th2-mediated “chronic inflammation” as result at least overproduction tumors. These data support prior observations regarding effect on cell function suggests consideration inhibitors future cancer immunotherapy studies