Down-regulation of HLA class I antigen-processing machinery components in esophageal squamous cell carcinomas: Association with disease progression

Abstract

Objective. Lack of human leukocyte antigen (HLA) presentation has been proposed to contribute to the immune evasion of cancer cells in some cancers including esophageal cancer. The aim of this study was to examine the expression of HLA class I antigen and the antigen-processing machinery (APM) components in esophageal squamous cell carcinoma (ESCC) lesions and to assess their association with histopathological characteristics. Material and methods. A total of 143 formalin-fixed, paraffin-embedded ESCC lesions collected in two hospitals in Shandong Province of China were studied. The expression levels were determined by immunohistochemistry. Results. TAP1, TAP2, LMP2, LMP7, β2m, and HLA class I antigen were lost or down-regulated in 30.8%, 35.0%, 45.0%, 48.0%, 56.0%, and 60.8% of the ESCC lesions tested, respectively. The loss of or down-regulated expressions of HLA class I, β2m, TAP1, LMP2, and LMP7 in tumor lesions were all significantly correlated to tumor grade and lymph node status. Expression of HLA class I antigens was strongly correlated to the expression levels of β2m, TAP1, TAP2, LMP2, and LMP7, suggesting APM component defects as a mechanism underlying HLA class I antigen down-regulation in ESCC lesions. Expression of APM components and HLA class I antigens was significantly associated with the extent of intratumoral T-cell infiltration. Conclusions. Our results indicate that lack or reduction of HLA class I antigens and expression of APM components in ESCC may render some tumor cells to escape the immunosurveillance mediated by CD8⁺ T cells and contribute to the clinical course of ESCC.

• Antigen-processing machinery
• cytotoxic T lymphocytes
• esophageal squamous cell carcinoma
• HLA class I
• immune surveillance