Interleukin-12 related cytokine gene expression at a tissue level in carcinomas of the larynx

Abstract

Head and neck squamous cell carcinomas are highly immunogenic tumors in which tumor-infiltrating lymphocytes (TIL) consist largely of CD4, Th1, and Th2 lymphocytes and a minor proportion of other immune effector cells, such as macrophages and B cells. Interleukin (IL)-12 release and antigen presentation from macrophages induce Th1 and Th2 differentiation. Gene expression for IL-12, interferon (IFN)γ, IL-4, and other cytokines was studied by reverse transcriptase–polymerase chain reaction in tissue sections from laryngeal carcinomas to evaluate the mechanisms of Th1 and Th2 lymphocyte differentiation. Local effects of cytokines were probed evaluating immunohistochemically the presence of inducible nitric oxide synthase positive tumor-infiltrating macrophages in 13 cases of laryngeal carcinomas. IL-12 gene expression was observed in five cases and that for IFNγ in nine cases. These cytokines were coexpressed in four specimens. IL-4 and transforming growth factor-β1 were detected in 5 and 11 cases, respectively. These findings show that IL-12, IFNγ, IL-4, and IL-6 in laryngeal carcinomas have different patterns of gene expression, suggesting distinct pathways of Th1 and Th2 lymphocyte differentiation to indicate that their exogenous modulation might be utilized in adoptive immunotherapy.