Head and neck squamous cell carcinoma (HNSCC) manipulates immune response

Abstract

Background Most surface epithelial precancers do not progress to advanced HNSCC, suggesting that host factors, such as the immune system, may interfere with HNSCC progression. HNSCC is believed to be immunosuppressive, although the mechanisms of HNSCC–immune system interactions are poorly understood. Dendritic cells (DC) play a central regulatory role in antitumor immunity. DC differentiate from monocytes and other precursors, and depending upon DC ability to mature they induce immunity or tolerance. Hypotheses Manipulation of host response is important for HNSCC progression. HNSCC factors regulate DC and DC precursor phenotype and activity. Study design In vitro cocultures and migration-function assays using HNSCC lines, normal monocytes, and DC were analyzed by flow cytometry and ELISA for cell phenotypes and cytokine production. Immunohistochemical evaluation was made of oral HNSCC specimens for DC, monocyte, and macrophage populations. Results In vitro, HNSCC lines produce cytokine interleukin-6 (IL-6) and Langerhans cell chemoattractant macrophage inflammatory protein-3α (MIP-3α), etc., as detected by ELISA. High IL-6–producing HNSCC further synergize with monocytes in IL-6 production, which correlates with monocyte differentiation into macrophages and leads to great synergism in VEGF production. In 2-chamber migration-function assays using DC and HNSCC introduced into separate chambers, high HNSCC MIP-3α production correlates with high DC numbers in HNSCC chambers, suggesting DC are recruited to HNSCC. However, DC maturation appears impaired. In cocultures, HNSCC support and expand specific DC populations. Monocyte, macrophage, and DC populations in HNSCC specimens are also evaluated. Conclusions HNSCC factors manipulate DC and DC precursor differentiation, migration, and function, which may support cancer progression.