Background: The purpose of this study was to elucidate IL-12Rβ2's roles as a tumor-associated immunological molecule, delineate the complex roles of IL-12Rβ2+ tumor-infiltrating lymphocytes (TILs) and tumor cell IL-12Rβ2 expression in the tumor microenvironment, and determine the correlation of IL-12Rβ2+ TILs and tumor cell IL-12Rβ2 expression with clinical prognosis.
Methods: We assessed mRNA and protein levels in matched laryngeal cancer tissues (LTs) and adjacent normal mucous membrane tissues (ANMMTs) from 3 laryngeal cancer (LC) patients and ratios of IL-12Rβ2+ TILs in matched LTs and ANMMTs from 61 LC patients. We used the Kaplan-Meier log-rank test and Cox regression hazard ratios to analyze survival.
Results: Comparative proteomic and transcriptomic assays revealed that matched LTs and ANMMTs from the 3 patients had significantly different IL-12Rβ2 and IFN-γ expression; the ratio of IL-12Rβ2+ TILs decreased with lower degrees of tumor differentiation. Among all 61 LC patients, the IL-12Rβ2+ TIL ratio in ANMMTs (38.5% ± 22.8%) was significantly higher than that in LTs (29.7% ± 19%; p<.001). Kaplan-Meier analysis revealed that patients with an IL-12Rβ2+ TIL ratio ≥35% had significantly better survival than those with an IL-12Rβ2+ TIL ratio <35% (log rank p=0.041). Multivariable analysis showed a significant association between a high IL-12Rβ2+ TIL ratio and overall survival (hazard ratio, 0.14; 95% confidence interval, 0.03-0.77).
Conclusion: Tumor cell differentiation is associated with TILs' expression of IL-12Rβ2, and an IL-12Rβ2+ TIL ratio ≥35%) indicates favorable prognosis in LC.
Keywords: Interleukin-12 receptor β2; Laryngeal squamous cell carcinoma; Prognosis; Tumor microenvironment; Tumor-infiltrating lymphocytes.
Copyright © 2017. Published by Elsevier Ltd.