Dendritic cells (DC) facilitate detachment of squamous carcinoma cells (SCC), while SCC promote an immature CD16+ DC phenotype and control DC migration

Lalitha V. Ramanathapuram, Dustin Hopkin, Zoya B. Kurago

Research output: Contribution to journalArticle

9 Scopus citations

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+CD86dim 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.

Original languageEnglish (US)
Pages (from-to)41-55
Number of pages15
JournalCancer Microenvironment
Volume6
Issue number1
DOIs
StatePublished - Apr 1 2013

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Keywords

  • CD16
  • Dendritic cells
  • Head and neck squamous cell carcinoma
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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