Down-regulation of HLA class I antigen processing molecules: an immune escape mechanism of renal cell carcinoma?

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.