Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity

Cancer immunosuppression evolves by constitution of an immunosuppressive network extending from a primary tumour site to secondary lymphoid organs and peripheral vessels and is mediated by several tumour-derived soluble factors (TDSFs) such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF). TDSFs induce immature myeloid cells and regulatory T cells in accordance with tumour progression, resulting in the inhibition of dendritic cell maturation and T-cell activation in a tumour-specific immune response. Tumour cells grow by exploiting a pro-inflammatory situation in the tumour microenvironment, whereas immune cells are regulated by TDSFs during anti-inflammatory situations—mediated by impaired clearance of apoptotic cells—that cause the release of IL-10, TGF-β, and prostaglandin E(2) (PGE(2)) by macrophages. Accumulation of impaired apoptotic cells induces anti-DNA antibodies directed against self antigens, which resembles a pseudo-autoimmune status. Systemic lupus erythematosus is a prototype of autoimmune disease that is characterized by defective tolerance of self antigens, the presence of anti-DNA antibodies and a pro-inflammatory response. The anti-DNA antibodies can be produced by impaired clearance of apoptotic cells, which is the result of a hereditary deficiency of complements C1q, C3 and C4, which are involved in the recognition of phagocytosis by macrophages. Thus, it is likely that impaired clearance of apoptotic cells is able to provoke different types of immune dysfunction in cancer and autoimmune disease in which some are similar and others are critically different. This review discusses a comparison of immunological dysfunctions in cancer and autoimmune disease with the aim of exploring new insights beyond cancer immunosuppression in tumour immunity

Modeling the commons as a game with vector payoffs

Since Hardin first formulated the tragedy of the commons, researchers have described various ways that commons problems are solved, all based on the model of individual rationality. Invariably, these institutional solutions involve creating some system of property rights. We formulate an alternative model, one not founded on property rights but on decision-making around so-called vector payoffs. The model is formalized and an existence proof provided. The new model is shown to be effective in explaining some anomalous results (e.g., unanticipated cooperation) in the experimental games literature that run counter to the rational model. We then use the case of the buffalo commons to illustrate how the new model affords alternative explanations for examples like the rise and fall of the buffalo herds in the Great Plains. We find the vector payoff model to complement, though not displace, that of individual rationality. © The Author(s) 2011.link_to_subscribed_fulltex

Three-dimensional ultrastructure of the septin filament network in Saccharomyces cerevisiae

Septins are essential for membrane compartmentalization and remodeling. Electron tomography of yeast bud necks shows filaments perpendicular and parallel to the mother-bud axis that resemble in vitro septin arrays. Filaments are still present, although disordered, in mutants lacking a single septin, underscoring the importance of septin assembly