The ninth International Conference of Anticancer Research, 6-10 October 2014, Sithonia, Greece.

The ninth conference of the International Institute for Anticancer Research, held in Sithonia, Greece in October 2014, included over 700 abstracts presented in 79 separate sessions and featured a wide range of topics in basic and clinical cancer research. This report describes a small but representative sample of these sessions. It covers some recent developments in research into the basic signal transduction pathways involved in carcinogenesis; a special session on the role of homeobox genes in cancer development; and clinical sessions covering advances in breast cancer, haematological cancers, and chemotherapy.

A large-scale computational study of inhibitor risk in non-severe haemophilia A.

Over 500 missense F8 mutations have been reported to cause non-severe haemophilia A. Some F8 genotypes appear to confer a higher risk of inhibitor formation than others and individuals with the same F8 genotype may have differing risks of inhibitor formation. We present an in silico strategy demonstrating the heterogeneity of factor VIII (FVIII)-derived antigen presentation whilst identifying patterns of human leucocyte antigen (HLA) peptide binding that might predict future inhibitor risk.

ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale.

The ultimate aim of the EU-funded ImmunoGrid project is to develop a natural-scale model of the human immune system-that is, one that reflects both the diversity and the relative proportions of the molecules and cells that comprise it-together with the grid infrastructure necessary to apply this model to specific applications in the field of immunology. These objectives present the ImmunoGrid Consortium with formidable challenges in terms of complexity of the immune system, our partial understanding about how the immune system works, the lack of reliable data and the scale of computational resources required. In this paper, we explain the key challenges and the approaches adopted to overcome them.

Proteins accessible to immune surveillance show significant T-cell epitope depletion: Implications for vaccine design.

T cell activation is the final step in a complex pathway through which pathogen-derived peptide fragments can elicit an immune response. For it to occur, peptides must form stable complexes with Major Histocompatibility Complex (MHC) molecules and be presented on the cell surface. Computational predictors of MHC binding are often used within in silico vaccine design pathways.

A computational Grid framework for immunological applications.

We have developed a computational Grid that enables us to exploit through a single interface a range of local, national and international resources. It insulates the user as far as possible from issues concerning administrative boundaries, passwords and different operating system features. This work has been undertaken as part of the European Union ImmunoGrid project whose aim is to develop simulations of the immune system at the molecular, cellular and organ levels.

Are bacterial vaccine antigens T-cell epitope depleted?

For many infectious diseases, protective immunity can be elicited by vaccination with pathogen-derived proteins. Peptides derived from these proteins are bound to major histocompatibility complex (MHC) molecules and presented to T-cell receptors to stimulate an immune response. We show here that, paradoxically, bacterial proteins known experimentally to elicit a protective immune response are relatively depleted in peptides predicted to bind to human MHC alleles.

Identification of the HLA-DM/HLA-DR interface.

Human leukocyte antigen (HLA)-DM is a critical participant in antigen presentation that catalyzes the dissociation of the Class II-associated Invariant chain-derived Peptide (CLIP) from the major histocompatibility complex (MHC) Class II molecules. There is competition amongst peptides for access to an MHC Class II groove and it has been hypothesised that DM functions as a 'peptide editor' that catalyzes the replacement of one peptide for another within the groove. It is established that the DM catalyst interacts directly with the MHC Class II but the precise location of the interface is unknown.

A novel predictive technique for the MHC class II peptide-binding interaction.

Antigenic peptide is presented to a T-cell receptor through the formation of a stable complex with a Major Histocompatibility Complex (MHC) molecule. Various predictive algorithms have been developed to estimate a peptide's capacity to form a stable complex with a given MHC Class II allele, a technique integral to the strategy of vaccine design. These have previously incorporated such computational techniques as quantitative matrices and neural networks.