Squamous Carcinoma Cells Influence Monocyte Phenotype and Suppress Lipopolysaccharide-Induced TNF-alpha in Monocytes

Abstract

Bacteria and chronic inflammation are present in squamous cell carcinoma of the head and neck (HNSCC), but their roles in the pathogenesis of HNSCC are unclear. Our studies described here revealed that human monocytes co-cultured short term with HNSCC cells were more likely to express CD16, and CD16+ small mononuclear cells were common in HNSCC specimens. In addition, we identified monocytes as the primary source of LPS-induced IL-6 and TNF-alpha in the monocyte-HNSCC co-cultures. Remarkably, relative to LPS-stimulated monocytes cultured alone, HNSCC cells profoundly suppressed LPS-induced TNF-alpha in monocytes, without compromising IL-6 production. High levels of cytoprotective factors like IL-6 and low levels of TNF-alpha are important for the tumor microenvironment that enables tumor cell survival, affects monocyte differentiation and may contribute to tumor colonization by bacteria. This study provides novel observations that HNSCC cells affect monocyte phenotype and function, which are relevant to the regulation of the HNSCC microenvironment.

Dendritic Cells (DC) Facilitate Detachment of Squamous Carcinoma Cells (SCC), While SCC Promote an Immature CD16+ DC Phenotype and Control DC Migration

“…We showed that HNSCC cells and their products can directly promote CD16 expression on monocytes in vitro [5]. CD16 + monocytes are known for their association with inflammatory states and preferentially differentiate into migratory DC [31,33].…”

“…It is very interesting that in the HNSCC microenvironment, monocyte lineage cells, including DC, express the low-affinity FcγRIII (CD16) [5], which can activate cells upon binding antigen-IgG antibody complexes [31,32]. We showed that HNSCC cells and their products can directly promote CD16 expression on monocytes in vitro [5].…”

“…Monocytes, Dendritic Cells (DC) Monocytes were prepared as described [4,5]. Monocytes were used as controls or differentiated into DC over 6 days with 1000 U/ml each GM-CSF and IL-4 (R&D Systems, Minneapolis, MN) in X-VIVO-15 at 37°C/7% CO 2 , with complete replacement of media and cytokines on alternate days.…”

“…Flow Cytometry was performed as described previously [5]. Data were collected on FACScan flow cytometer using CellQuest software and analyzed using FlowJo software (TreeStar, Ashland, OR).…”

“…The mechanisms that regulate HNSCC pathogenesis, particularly those pertaining to the tumor microenvironment are poorly defined. The microenvironment of HNSCC is characterized by dense infiltrates of immune system cells, including monocyte lineage cells [4][5][6], such as CD68…”