Human leukocyte antigen expression in renal cell carcinoma lesions does not predict the response to interferon therapy.

V Mattijssen, J Van Moorselaar, P H De Mulder, L Schalkwijk, D J Ruiter
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引用次数: 11

Abstract

Human leukocyte antigen (HLA) classes I and II molecules are essential for antigen presentation to cytotoxic T cells and helper T cells, respectively. Consequently, they may play a role in anticancer immunotherapy as well. We studied whether the pretreatment HLA phenotype of the tumor is predictive for response to interferon immunotherapy in vivo. Therefore, renal cell carcinoma (RCC) primary tumor lesions from 31 patients treated with interferon-alpha and interferon-gamma (13 responders and 18 nonresponders) were analyzed retrospectively for HLA antigen expression with immunohistochemical methods. Furthermore, from eight patients, pretreatment metastatic lesions were examined. In the primary tumors HLA class I expression was high: in 26 of 30 lesions more than 50% cells were stained. HLA class II expression was mostly low: in 14 of 31 primary tumors less than 5% cells were stained. A significant correlation was found between HLA phenotype of primary tumors and corresponding metastases. There was no association between tumor HLA classes I and II antigen expression and clinical response to interferon therapy. In conclusion, pretreatment HLA phenotype of RCC has no predictive value for outcome of interferon immunotherapy. A role for treatment-induced changes in HLA expression in vivo, however, can not be excluded. These findings do not provide indications for the working mechanism of interferon immunotherapy in vivo.

人白细胞抗原表达在肾细胞癌病变不能预测对干扰素治疗的反应。
人类白细胞抗原(HLA) I类和II类分子分别是向细胞毒性T细胞和辅助T细胞呈递抗原所必需的。因此,它们也可能在抗癌免疫治疗中发挥作用。我们研究了肿瘤的预处理HLA表型是否能预测体内对干扰素免疫治疗的反应。因此,我们采用免疫组织化学方法回顾性分析了31例接受干扰素- α和干扰素- γ治疗的肾细胞癌(RCC)原发肿瘤病变(13例有反应,18例无反应)的HLA抗原表达。此外,对8例患者进行了预处理转移灶检查。在原发肿瘤中,HLA I类表达高:30个病变中有26个超过50%的细胞被染色。HLAⅱ类表达多数较低:31例原发肿瘤中有14例细胞染色低于5%。原发性肿瘤的HLA表型与相应的转移有显著的相关性。肿瘤HLA I类和II类抗原表达与临床对干扰素治疗的反应无相关性。结论:肝癌前HLA表型对干扰素免疫治疗结果无预测价值。然而,不能排除治疗引起的体内HLA表达变化的作用。这些发现并不能说明干扰素免疫治疗在体内的作用机制。
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