Deficient expression of human leukocyte antigen class I antigen-processing machinery components in human esophageal squamous cell carcinoma.

Human leukocyte antigen (HLA) class I antigen-processing machinery components defects are found in many tumors, which may have a negative impact on the outcome of T-cell based immunotherapy. Scant information is available about antigen-processing machinery component expression in esophageal squamous cell carcinoma (ESCC). Here, we investigated that HLA class I, β2-microglobulin (β2m), and transporter associated with antigen processing subunit (TAP1) expression in 160 formalin-fixed and paraffin-embedded esophageal lesions (120 primary ESCC and 40 matched lymph node metastases) in a tissue microarray by immunohistochemical staining. A synchronous downregulation of HLA class I, β2m, and TAP1 was observed in 57.3% of primary and 64.7% of metastatic lesions. And at least one of these three molecules exhibited an impaired expression in all metastatic and 95% of primary ESCC lesions. Only TAP1 expression was more frequently (P < 0.001) downregulated in metastatic than in primary ESCC lesions, and significantly (P < 0.05) associated with tumor grade. HLA class I, β2m, and TAP1 expression was more frequently downregulated in primary ESCC lesions with lymph node metastasis than those without lymph node metastasis (HLA class I: P = 0.003, β2m: P = 0.034, and TAP1: P = 0.028). Our findings suggest that abnormalities of HLA class I, β2m, and TAP-1 expression is a frequent event in ESCC, which might provide ESCC cells with a mechanism to escape from cytotoxic T lymphocyte recognition. The present study emphasizes the need to evaluate the antigen-processing pathway in ESCC patients, particularly in those selected for T-cell based immunotherapies. [ABSTRACT FROM AUTHOR]