title: Dendritic Cells (DC) Facilitate Detachment of Squamous Carcinoma Cells (SCC), While SCC Promote an Immature CD16(+) DC Phenotype and Control DC Migration.
abstract: In the inflammatory mucosal microenvironment of head and neck SCC (HNSCC), DC 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 two established HNSCC cell lines that represent well- and poorly-differentiated SCC, respectively, we found that carcinoma cells induced significant increases in CD16 expression on DC while promoting a CD1a(+)CD86(dim) immature phenotype, similar to that observed in HNSCC specimens. Moreover, HNSCC cells affected steady-state and CCL21-induced migration of DC, and these effects were donor-dependent. The CCL21-induced migration directly correlated with HNSCC-mediated effects on CCR7 and CD38 expression on DC-SIGN-high DC. The dominant pattern seen in six out of nine donors was the increase in steady-state and CCL21-induced DC migration in co-cultures with HNSCC, while the reverse pattern, i.e., decreased DC migration in co-cultures with SCC, was identified in two donors. A split in migratory DC behavior, i.e. increase with one HNSCC cell line and a decrease with the second cell line, was observed in one donor. 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 novel insights into the effects of DC-HNSCC interactions relevant to the tumor microenvironment.
authors.affiliation: Oral and Maxillofacial Pathology, Radiology and Medicine, College of Dentistry, New York University, 345 E. 24th St., Rm 837S, 1010S, New York, NY, 10010, USA.
authors.forename: Lalitha V
authors.initials: LV
authors.lastname: Ramanathapuram
authors.forename: Dustin
authors.initials: D
authors.lastname: Hopkin
authors.forename: Zoya B
authors.initials: ZB
authors.lastname: Kurago