Atkins Derek, Ferrone Soldano, Schmahl Gerd E, Störkel Stefan, Seliger Barbara
IIIrd Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany.
J Urol. 2004 Feb;171(2 Pt 1):885-9. doi: 10.1097/01.ju.0000094807.95420.fe.
Proper HLA class I antigen processing and presentation is a prerequisite for the recognition of tumor cells by cytotoxic T lymphocytes. To date there exist only limited information on the expression of components of the HLA class I associated antigen processing machinery (APM) in surgically removed benign renal cell adenoma, and primary and metastatic renal cell carcinoma (RCC).
A total of 133 primary RCCs of different subtypes, 10 renal cell adenoma biopsies, 32 matched metastases of different localization and autologous normal kidney epithelium were immunohistochemically analyzed for the expression of HLA class I antigens, low molecular weight protein (LMP)2 and LMP7, the transporter associated with antigen processing subunit (TAP1) and beta 2-microglobulin (beta 2-m).
Normal kidney tissue showed strong cytoplasmic staining intensity for LMP2, LMP7 and TAP1, whereas beta 2-m and HLA class I heavy chains were detected on the cell surface. A low frequency of HLA class I HC and beta 2-m down-regulation was found in RCC. In contrast, primary RCC and metastases showed a high frequency of a total lack of heterogeneous TAP1, LMP2 and LMP7 expression, which was often coordinately regulated. APM component deficiencies were associated with RCC subtypes but not with tumor grading and staging.
HLA class I APM component abnormalities appear to represent an immune escape mechanism of RCC. This finding emphasizes the need to evaluate the integrity and expression of these molecules in patients with RCC, especially in those selected for treatment with T-cell based immunotherapy.
正确的HLA I类抗原加工与呈递是细胞毒性T淋巴细胞识别肿瘤细胞的前提条件。迄今为止，关于在手术切除的良性肾细胞腺瘤、原发性和转移性肾细胞癌（RCC）中HLA I类相关抗原加工机制（APM）各组分的表达情况，仅有有限的信息。
对133例不同亚型的原发性RCC、10例肾细胞腺瘤活检组织、32例不同部位的配对转移灶以及自体正常肾上皮进行免疫组织化学分析，检测HLA I类抗原、低分子量蛋白（LMP）2和LMP7、抗原加工相关转运体亚基（TAP1）以及β2-微球蛋白（β2-m）的表达。
正常肾组织中LMP2、LMP7和TAP1呈现强细胞质染色强度，而β2-m和HLA I类重链在细胞表面被检测到。在RCC中发现HLA I类重链和β2-m下调的频率较低。相比之下，原发性RCC和转移灶显示出TAP1、LMP2和LMP7完全缺乏异质性表达的高频率情况，且这种情况通常是协同调节的。APM组分缺陷与RCC亚型相关，但与肿瘤分级和分期无关。
HLA I类APM组分异常似乎代表了RCC的一种免疫逃逸机制。这一发现强调了评估RCC患者中这些分子的完整性和表达的必要性，特别是对于那些选择基于T细胞的免疫疗法进行治疗的患者。
