RESUMO
BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), the secretion of various immunosuppressive mediators contributes to large-scale effects on the immune functions. The influence of HNSCC on various cellular functions of human myeloid dendritic cells (MDC) was analyzed in this work. MATERIALS AND METHODS: MDCs were isolated from peripheral blood by 'magnetic bead separation'. Cellular functions were analyzed using flow cytometry, migration- and ELISPOT assays as well as cytokine detection assays. RESULTS: HNSCC massively affects MDCs to induce effective T-cell responses. Analysis of MDC migration and cytokine secretion revealed that HNSCC triggers the production of tumor-promoting and immunosuppressive cytokines IL-1 and IL-10 and results in an increased MDC migration activity. CpG-ODN is able to act contradictory to HNSCC. CONCLUSION: HNSCC is able to modulate various functions of human MDCs. CpG-ODN is suggested as a potential immunostimulatory agent of human MDC.
Assuntos
Carcinoma de Células Escamosas/imunologia , Células Dendríticas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Movimento Celular/imunologia , Ilhas de CpG/genética , Células Dendríticas/citologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imunofenotipagem , Interleucina-6/biossíntese , Interleucinas/biossíntese , Interleucinas/metabolismo , Ativação Linfocitária , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/imunologia , Oligonucleotídeos/genética , Oligonucleotídeos/farmacologia , Linfócitos T/imunologiaRESUMO
BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), a variety of immunomodulatory mediators contribute to strongly impaired immune functions. The secretion of C-reactive protein (CRP) by HNSCC cells and its influence on human myeloid dendritic cells (MDC) was investigated. MATERIALS AND METHODS: The CRP levels were analyzed using photometric methods and real-time PCR. The MDC were isolated from peripheral blood by 'magnetic bead separation' and incubated with different CRP concentrations. The CRP isoforms were analyzed by native PAGE (polyacrylamide gel electrophoresis). The cells were analyzed using migration assays and flow cytometry. RESULTS: HNSCC cell lines were able to autonomously express C-reactive protein. Pentameric CRP triggered the down-regulation of chemokine receptor CCR5 and led to a decreased migration of human MDC. CONCLUSION: CRP appeared to be a modulator of the migration activity of human MDC. The functional modulation of immune cells represents a crucial immune escape mechanism of human carcinomas.
