An Antimicrobial Peptide Regulates Tumor-Associated Macrophage Trafficking via the Chemokine Receptor CCR2, a Model for Tumorigenesis

Tumor-associated macrophages (TAMs) constitute a significant part of infiltrating inflammatory cells that are frequently correlated with progression and poor prognosis of a variety of cancers. Tumor cell-produced human β-defensin-3 (hBD-3) has been associated with TAM trafficking in oral cancer; however, its involvement in tumor-related inflammatory processes remains largely unknown., applying a cross-desensitization strategy of CCR2 and its pharmacological inhibitor (RS102895), respectively, was also carried out. outcome and demonstrates the importance of the innate immune system in the development of tumors

Interaction Between Natural Killer and Dendritic Cells: the Role of CD40, CD80 and Major Histocompatibility Complex Class I Molecules in Cytotoxicity Induction and Interferon-gamma Production

This study focuses on the differential role of CD40 and CD80 costimulatory molecules and major histocompatibility complex class I (MHC-I) antigens in the regulation of the interplay between dendritic cells (DCs) and interleukin (IL)-2-activated human natural killer (NK) lymphocytes. Our data indicate that CD40 and CD80 molecules might play a preferential role in the induction of cytotoxic function but not in the interferon-gamma(IFN-gamma) production by human IL-2-activated NK effectors in the presence of autologous and allogeneic DCs. In addition, a critical role of CD94-dependent MHC-I recognition in the regulation of both IFN-gamma production and target cell lysis was shown in the functional interaction between NK and DCs

Interaction between natural killer and dendritic cells: the role for CD40, CD80 and Major Histocompatibility Complex class I molecules in cytotoxicity induction and Interferon-gamma production

This study focuses on the differential role of CD40 and CD80 costimulatory molecules and major histocompatibility complex class I (MHC-I) antigens in the regulation of the interplay between dendritic cells (DCs) and interleukin (IL)-2-activated human natural killer (NK) lymphocytes. Our data indicate that CD40 and CD80 molecules might play a preferential role in the induction of cytotoxic function but not in the interferon-gamma(IFN-gamma) production by human IL-2-activated NK effectors in the presence of autologous and allogeneic DCs. In addition, a critical role of CD94-dependent MHC-I recognition in the regulation of both IFN-gamma production and target cell lysis was shown in the functional interaction between NK and DCs

Lipopolysaccharide-Squamous Cell Carcinoma-Monocyte Interactions Induce Cancer-Supporting Factors Leading to Rapid STAT3 Activation

Oral and oro-pharyngeal squamous cell carcinomas (OSCC) exhibit surface breach, and recent studies have demonstrated bacterial contamination of primary and metastatic OSCC. Increasing concentrations of inflammatory products, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), correlate with, and contribute to, cancer progression, but their regulation in OSCC is poorly understood. We hypothesized that monocyte-lineage cells and bacterial contamination may contribute important inflammatory products that can support OSCC progression. We found that relative to non-specific chronic mucositis, oral carcinoma-in-situ/superficially-invasive OSCC contained more monocyte-lineage cells. In vitro, we used lipopolysaccharide (LPS) to model bacterial contamination, and evaluated the effects of oral and oropharyngeal (O)SCC-monocyte interactions and of LPS on OSCC cells and on the production of IL-6 and VEGF. OSCC cell lines varied in constitutive cytokine and chemokine production, and OSCC-monocyte interactions in the absence of LPS stimulated IL-6 and VEGF occasionally, while LPS-OSCC-monocyte interactions were always strongly stimulatory. Importantly, LPS independently stimulated some OSCC lines to secrete monocyte-dendritic cell chemoattractants CCL2 and/or CCL20, as well as IL-6 and/or VEGF. While very little constitutive Y705-STAT3 phosphorylation (pY705-STAT3) was detectable in HNSCC lines, IL-6 rapidly induced pY705-STAT3 in OSCC lines that produced little IL-6 constitutively. Supernatants from LPS-OSCC-monocyte co-cultures always rapidly and strongly activated STAT3, which was partly due to IL-6. We conclude that monocytes and microbial contamination have the potential to contribute to OSCC progression, as STAT3 activation in OSCC cells depends on soluble factors, which are consistently available through LPS-OSCC-monocyte interactions