The immunosuppressive factors IL-10,TGF-β,and VEGF do not affect the antigen-presenting function of CD40-activated B cells

Background: progress in recent years strengthened the concept of cellular tumor vaccinations. however,a crucial barrier to successful cancer immunotherapy is tumor-mediated immunosuppression. tumor-derived soluble factors such as il-10,tgf-β,and vegf suppress effector cells either directly or indirectly by disruption of dendritic cell (dc) differentiation,migration and antigen presentation. human b cells acquire potent immunostimulatory properties when activated via cd40 and have been shown to be an alternative source of antigen-presenting cells (apcs) for cellular cancer vaccines. nevertheless,in contrast to dcs little knowledge exists about their susceptibility to tumor derived immunosuppressive factors. thus,we assessed whether il-10,tgf-β,or vegf do affect key aspects of the immunostimulatory function of human cd40-activated b cells. methods: cell surface expression of adhesion and costimulatory molecules and the proliferation capacity of cd40- activated b cells were compared to untreated controls by flow cytometry. migration towards important chemokines of secondary lymph organs was measured with or without exposure to the immunosuppressive cytokines. finally,an influence on t cell stimulation was investigated by allogeneic mixed lymphocyte reactions. for statistical analysis students t test or two-way analysis of variance followed by bonferroni's post-hoc test was used to compare groups. p values of ≤0.05 were considered statistically significant. results: neither cell adhesion nor the expression of mhc class ii and costimulatory molecules cd80 and cd86 was inhibited by addition of il-10,tgf-β,or vegf. likewise,the proliferation of cd40-activated b cells was not impaired. despite being exposed to il-10,tgf-β,or vegf the b cells migrated equally well as untreated controls to the chemokines slc and sdf-1α. most importantly,the capacity of cd40-activated b cells to stimulate cd4+ and cd8+ t cells remained unaffected. conclusion: our findings suggest that key immunostimulatory functions of cd40-activated b cells are resistant to inhibition by the immunosuppressive factors il-10,tgf-β,and vegf. this supports considerations to use ex vivo generated cd40-activated b cells as a promising alternative or additional apc for cellular immunotherapy,especially in settings where these immunosuppressive cytokines are present in tumor environment. © 2012 shimabukuro-vornhagen et al.; licensee biomed central ltd.