Abstract In the inflammatory mucosal microenvironment of head and neck squamous cell carcinoma (HNSCC), dendritic cells (DC) are prominent; they express CD16, and are usually in direct contact with tumor cells. Mucosal and inflammation-associated DC develop from monocytes, and monocyte-derived DC are used in HNSCC immunotherapy. However, beyond apoptotic tumor cell uptake and presentation of tumor antigens by DC, HNSCC cell interactions with DC are poorly understood. Using co-cultures of monocyte-derived DC and established HNSCC cell lines we found that carcinoma cells induced significant increases in CD16 expression on DC while promoting a CD1a+CD86dim immature phenotype, similar to that observed in HNSCC specimens. Moreover, HNSCC cells strongly affected DC migration, both steady-state and CCL21-induced. The effects of carcinoma cells on migration were donor-dependent, and CCL21-induced migration directly correlated with HNSCC-mediated effects on CCR7 and CD38 expression on DC. Most remarkably, the numbers of live detached HNSCC cells were orders of magnitude higher in DC-HNSCC co-cultures than in parallel HNSCC cell cultures without DC. This study provides a novel insight into the outcomes of DC-HNSCC interactions relevant to the tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1395. doi:10.1158/1538-7445.AM2011-1395