Antigen peptide transporters are upregulated in squamous cell carcinoma of the oral tongue and show sex-specific associations with survival

Abstract

Transporter associated with antigen processing 1 (TAP1) and TAP2 serve pivotal roles in adaptive immunity. Tumor cells often show reduced antigen presentation on their surface as one mechanism to escape immune recognition. Whether downregulation of TAPs is a common mechanism of tumor immune evasion in squamous cell carcinoma of the oral tongue (SCCOT) is unclear. In the present study, samples from 78 patients with SCCOT and 17 patients with benign hyperplastic tongue lesions were analyzed for TAP1 and TAP2 expression by immunohistochemistry. The percentage of positive cells and staining intensity were scored. Associations with clinicopathological variables and survival outcome were also investigated. The results demonstrated that TAP1 and TAP2 levels were highly associated with each other in individual samples and were upregulated in SCCOT compared with benign lesions (P<0.001). The proportion of TAP1- or TAP2-positive tumor cells was >80% in all but two of the tumors, whereas 25.6 and 23.0% of the tumors showed weak intensity of TAP1 and TAP2, respectively. There were no significant associations with clinicopathological variables or survival outcomes between TAP-intermediate/strong and TAP-weak tumors. However, in patients <70 years old and with early stage SCCOT, male patients had better outcomes than female patients (log-rank P<0.05), and the best outcome was observed in male patients with intermediate/strong TAP expression. In conclusion, loss of TAP was not a frequent event in SCCOT and stronger TAP expression in male patients was associated with improved survival, providing further evidence for sex-specific immune modulation in cancer.

Keywords: immune evasion; sex; squamous cell carcinoma of the oral tongue; tongue; transporter associated with antigen processing 1; transporter associated with antigen processing 2.

Figure 1.

Immunohistochemical staining of TAP1 and TAP2 in tumors and benign lesions. Representative results of (A) weak, (B) intermediate and (C) strong staining intensity of TAP1 in SCCOT, and (D) weak staining intensity of TAP1 in hyperplastic lesion. Corresponding staining results for TAP2 are (E) weak, (F) intermediate and (G) strong in SCCOT and (H) weak in hyperplastic lesion. SCCOT, squamous cell carcinoma of the oral tongue; TAP, transporter associated with antigen processing.

Figure 2.

Effect of TAP1 levels on patient survival. Kaplan-Meier curves showing no difference in (A) overall survival, (B) cancer-specific survival or (C) disease-free interval between TAP1-weak (n=20) and TAP1-intermediate/strong (n=58) patients. The P-values for the log-rank tests are shown. Cum, cumulative; TAP, transporter associated with antigen processing.

Figure 3.

Effect of sex on survival outcome in patients under 70 years of age. For patients with early stage SCCOT, Kaplan-Meier curves indicate the effect of sex on (A) overall survival, (B) cancer-specific survival and (C) disease-free interval. For patients with late-stage SCCOT, there is no effect of sex on (D) overall survival, (E) cancer-specific survival and (F) disease-free interval. The P-values for the log-rank tests are shown. Cum, cumulative; SCCOT, squamous cell carcinoma of the oral tongue.

Figure 4.

Effect of sex and TAP on survival outcome in patients under 70 years and with early-stage squamous cell carcinoma of the oral tongue. Kaplan-Meier curves showing the impact of sex and TAP1-intensity on (A) overall survival, (B) cancer-specific survival and (C) disease-free interval. Impacts of sex and TAP2-intensity on (D) overall survival, (E) cancer-specific survival and (F) disease-free interval. The P-values for the log-rank tests comparing survival among the four groups are shown. For TAP2 and cancer-specific survival, no statistics were calculated because all cases are censored. Cum, cumulative; TAP, transporter associated with antigen processing.