Torisu-Itakura Hitoe, Lee Jonathan H, Huynh Young, Ye Xing, Essner Richard, Morton Donald L
Department of Molecular Therapeutics, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, 90404, USA.
J Immunother. 2007 Nov-Dec;30(8):831-8. doi: 10.1097/CJI.0b013e318158795b.
There are no standard methods to predict response to treatment or outcome of stage IV melanoma. Our previous assessment of peripheral blood mononuclear cells (PBMC) from immunized patients demonstrated that interleukin (IL)-10 expression might be associated with prognosis. However, PBMC are a mixture of CD4+ cells, CD8+ cells, and monocytes. This study identified the subset of PBMC responsible for IL-10 expression and evaluated the prognostic value of IL-10 expression in immunized stage IV patients. Eighty-seven patients with stage IV melanoma were randomly selected from our database. All patients had received an allogeneic melanoma whole-cell vaccine (Canvaxin) after complete resection of clinical disease. Blood samples had been collected serially during Canvaxin administration and cryopreserved. Intracellular IL-10 expression was assessed by double staining fluorescence-activated cell sorter. CD14+ monocytes are the predominant PBMC producing IL-10. Sixteen weeks after treatment (week 16), IL-10 levels were significantly (P=0.02) higher in poor-survival patients than those with favorable outcomes. Patients were separated into 2 groups on the basis of the CD14+ monocyte IL-10 response: either increasing or decreasing IL-10 expression from preimmunization (week 0) to week 16 blood draws. Patients with increasing IL-10 levels had significantly shorter survival than those whose IL-10 levels decreased at week 16 (P<0.0001). Multivariate analysis demonstrated that trends in IL-10 levels inversely correlated with survival (P<0.0001). We conclude that CD14+ monocytes are the dominant cellular source of IL-10 among PBMC and that changes in IL-10 expression may serve as an immunologic-based surrogate for predicting outcome for stage IV patients after surgical resection.
目前尚无预测IV期黑色素瘤治疗反应或预后的标准方法。我们之前对免疫治疗患者外周血单个核细胞（PBMC）的评估表明，白细胞介素（IL）-10表达可能与预后相关。然而，PBMC是CD4+细胞、CD8+细胞和单核细胞的混合物。本研究确定了负责IL-10表达的PBMC亚群，并评估了免疫治疗的IV期患者中IL-10表达的预后价值。从我们的数据库中随机选取87例IV期黑色素瘤患者。所有患者在临床疾病完全切除后均接受了同种异体黑色素瘤全细胞疫苗（Canvaxin）。在接种Canvaxin期间连续采集血样并冷冻保存。通过双染色荧光激活细胞分选仪评估细胞内IL-10表达。CD14+单核细胞是产生IL-10的主要PBMC。治疗16周后（第16周），生存较差患者的IL-10水平显著（P=0.02）高于预后良好的患者。根据CD14+单核细胞IL-10反应将患者分为两组：从免疫前（第0周）到第16周采血时IL-10表达增加或减少。IL-10水平升高的患者生存时间明显短于第16周时IL-10水平下降的患者（P<0.0001）。多变量分析表明，IL-10水平的变化趋势与生存率呈负相关（P<0.0001）。我们得出结论，CD14+单核细胞是PBMC中IL-10的主要细胞来源，IL-10表达的变化可作为预测手术切除后IV期患者预后的基于免疫的替代指标。
