Mattijssen V, Van Moorselaar J, De Mulder P H, Schalkwijk L, Ruiter D J
Department of Medicine, University Hospital Nijmegen, The Netherlands.
J Immunother (1991). 1992 Jul;12(1):64-9. doi: 10.1097/00002371-199207000-00008.
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.
人类白细胞抗原（HLA）I类和II类分子分别对于向细胞毒性T细胞和辅助性T细胞呈递抗原至关重要。因此，它们在抗癌免疫治疗中可能也发挥作用。我们研究了肿瘤的预处理HLA表型是否可预测体内对干扰素免疫治疗的反应。为此，采用免疫组化方法对31例接受α干扰素和γ干扰素治疗的患者（13例反应者和18例无反应者）的肾细胞癌（RCC）原发性肿瘤病灶进行了HLA抗原表达的回顾性分析。此外，对8例患者的预处理转移病灶进行了检查。在原发性肿瘤中，HLA I类表达较高：30个病灶中有26个病灶超过50%的细胞被染色。HLA II类表达大多较低：31例原发性肿瘤中有14例少于5%的细胞被染色。原发性肿瘤的HLA表型与相应转移灶之间存在显著相关性。肿瘤HLA I类和II类抗原表达与干扰素治疗的临床反应之间无关联。总之，RCC的预处理HLA表型对干扰素免疫治疗的结果没有预测价值。然而，不能排除体内HLA表达的治疗诱导变化所起的作用。这些发现未为干扰素免疫治疗在体内的作用机制提供线索。
