Defects In The Human Leukocyte Antigen Class I Antigen-Processing Machinery In Head And Neck Squamous Cell Carcinoma: Association With Clinical Outcome

Background & Aim:The first part of experiment,we have investigated the role of antigen-processing machinery(APM) component defects in HLA classⅠantigen down-regulation in laryngeal squamous cell carcinoma(SCC) lesions and assessed the clinical significance of these defects.The second part of experiment,the purpose of this study was to determine whether HLA classⅠantigen and TAP-1 were down-regulated in squamous cell carcinoma of the head and neck(SCCHN) and to explore the significance of them for evading host immunosurveillance.Methods:Fifty-one formalin-fixed,paraffin-embedded tumor lesions were examined for APM component TAP-1,LMP-7 and HLA classⅠantigen expression by immunohistochemistry.All patients were regularly followed up and the clinical data were collected systematically.Western immunoblotting were used to assess the expression of HLA classⅠantigen and TAP-1 in 30 cases of head and neck tissue and adjacent normal tissue.Results:The first part of experiment:HLA classⅠantigens,TAP-1 and LMP-7 were down-regulated in 56.9%(29/51),39.2%(20/51),45.1%(23/51) of the lesions tested respectively,whereas HLA classⅠantigens,TAP-1 and LMP-7 were lost in 21.6%(11/51),33.3%(17/51),27.5%(14/51)of the lesions tested respectively. TAP-1 and LMP-7 expression was significantly correlated with HLA classⅠantigen expression(r=0.460,P＜0.05 and r=0.685,P＜0.05,respectively).HLA classⅠantigens down-regulation was significantly correlated with T stage(P＜0.05).Both TAP-1 and LMP-7 down-regulation were significantly correlated with T stage and TNM stage(P＜0.05)。Furthermore,LMP-7 and HLA classⅠantigen down-regulation were significantly associated with reduced patients' overall survival(P＜0.05) and disease-free survival(P＜0.05).With multivariate analysis,lymph nodes metastasis, recurrence and HLA classⅠantigen down-regulation were unfavorable prognostic factors(P＜0.05).The second part of experiment:Immunoblotting.demonstrated that HLA classⅠantigen and TAP-1 protein were lower in 30 cases of SCCHN compared with adjacent normal mucosa.The integral optical density(IOD) of HLA classⅠantigen protein in 30 cases of SCCHN were significantly decreased,compared with those of normal tissues(P＜0.05).And the integral optical density(IOD) of TAP-1 protein in 30 cases of SCCHN were also significantly decreased,compared with those of normal tissues (P＜0.01).Conclusion:HLA classⅠantigen and APM component down-regulation occur frequently in SCCHN.Alteration in HLA classⅠantigen and APM component expression may be used by cancer cells to avoid immune surveillance,while HLA classⅠantigen down-regulation is a major contributing factor to tumour progression and mortality.HLA classⅠantigen and APM component TAP-1,LMP-7 expression in SCCHN lesions may be play an impotent role on tumor immunosurveillance and in the course of the disease.