Showing papers by "Silvano Sozzani published in 2011"

Plasmacytoid dendritic cells and cancer.

Abstract: Cancer develops in a complex microenvironment comprising cancer cells, stromal cells, and host immune cells with their soluble products. The counteracting host-protective and tumor-promoting roles of different immune cell populations have been elegantly clarified in the last decade by pertinent genetically modified mouse models. Among cells with a potential role in cancer immunity, PDCs might represent important players as a result of their capacity to bring together innate and adaptive immunity. This review summarizes current knowledge about the role of PDCs in cancer immunity. PDCs have been documented in primary and metastatic human neoplasms; however, the clinical significance of this finding is still unknown. Once into the tumor bed, PDCs can be hijacked by the tumor microenvironment and lose their propensity to produce the required amount of endogenous I-IFN. However, when properly reprogrammed (i.e., by TLR agonists), PDCs might mediate tumor rejection in a clinical setting. Tumor rejection, at least partially, is driven by I-IFN and seems to require a cross-talk with other innate immune cells, including IFN DCs. The latter evidence, although still limited to skin cancers, can provide a leading model for developing adjuvant immune therapy for other neoplasms. To this end, the generation of appropriate mouse models to modulate the frequency and activation state of murine PDCs will also be of remarkable importance.

Langerhans cell histiocytosis: a cytokine/chemokine-mediated disorder?

Abstract: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by an abnormal accumulation and/or proliferation of cells with a Langerhans cell phenotype. Although no clear cause of LCH has been identified, it has been postulated that LCH might be the consequence of an immune dysregulation, causing Langerhans cells to migrate to and accumulate at various sites. Production of cytokines and chemokines is a central feature of immune regulation. Cytokines are abundantly present within LCH lesions. We review here the potential role of cytokines and chemokines in the pathogenesis of LCH. The type, distribution, and number of different cytokines released within lesions can provide clues to the possible aetiology of LCH and, ultimately, might offer therapeutic possibilities using recombinant cytokines or antagonists for this disorder.

OM-85 shapes dendritic cell activation into a “pre-alert” phenotype

Abstract: Background: OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®) has proven efficacy in the prevention of recurrent infections of the airways and acute exacerbations in COPD. OM-85 is a lyophilized bacterial extract comprising fractions of 21 different inactivated bacterial strains. Previous work has shown that OM-85 acts as an immunostimulant, and that it may act on human dendritic cells (hDC). However, the molecular mechanisms through which OM-85 activates hDC remained largely unknown. Aims: Investigate the impact of OM-85 stimulation on hDC and identify the immune receptors implicated in OM-85 response. Methods: Primary and in vitro derived hDC were used to determine the precise OM-85 effects on DC biology. Stably transfected cell lines expressing human receptors were used to characterize OM-85 receptor-dependent activity. Results: In hDC, OM-85 induced the secretion of IL-6 and of several chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) with a potency comparable to the prototypical activating stimulus LPS. OM-85 potentiated the effect of IFNγ in terms of IL-6, IL-12 and IL-10 release. The induction of selected chemokines by suboptimal doses of classical pro-inflammatory stimuli were boosted by the presence of OM-85. In addition, it was identified that OM-85 activates TLR2, NOD1 and NOD2 receptors in a significant, dose-response manner. Conclusions: OM-85 induces a mild and well shaped hDC activation through selected pattern recognition receptors. This activation may contribute to the generation of a “pre-alert state” resulting in an early protection towards incoming infection. These results provide new insights in the understanding of the mode of action of OM-85, opening new venues for further investigation.