Downregulation of expression of transporters associated with antigen processing 1 and 2 and human leukocyte antigen I and its effect on immunity in nasopharyngeal carcinoma patients

鼻咽癌患者抗原加工相关转运蛋白1和2以及人类白细胞抗原I表达下调及其对免疫的影响

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Abstract

The human leukocyte antigen (HLA)-I and antigen-processing machinery (APM) are crucial in the anti-cancer immune response. The aim of this study was to assess the clinical significance of the APM components [transporters associated with antigen processing (TAP)-1 and -2 and HLA-I] in nasopharyngeal carcinoma (NPC). A total of 58 NPC specimens and 20 healthy specimens used as control were evaluated by semiquantitative immunohistochemistry for three APM components (TAP-1, TAP-2 and HLA-I). The expression of the APM components in NPC was downregulated. CD4(+) and CD8(+) T cells were measured by flow cytometry and IL-10 was measured by ELISA. The number of CD8(+) T cells and the expression of IL-10 were higher and the number of CD4(+) T cells was lower in NPC, compared to the controls. The number of CD8(+) T cells and the expression of IL-10 were negatively correlated with TAP-1, TAP-2 and HLA-I expression. The clinical phase, lymph node metastasis, distant metastasis, pathological type, TAP-1 expression, TAP-2 expression and HLA-I expression were identified as prognostic factors by the Kaplan-Meier analysis. A multivariate analysis using a Cox regression model indicated that distant metastasis and the downregulation of HLA-I expression were independent unfavorable prognostic factors. In conclusion, the lower expression of HLA-I induced immunosuppression in NPC patients and was associated with a poor prognosis.

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