Playing in three makes it simpler: mapping the cognitive figure-ground framework onto cancer-immunology and...

The avalanche of research findings in complex multidisciplinary fields, such as cancer immunobiology, requests organizing and practical working models for scientists and clinicians. Frameworks from one scientific discipline can be adopted for another one, to clarify and provide new insights into complex findings. A 'figure-ground' (FG) perspective was adopted from cognitive sciences to construct a simple organizing tool, which can assist in understanding tumour development and immunotherapy designing. In an FG arena, there is a figure that needs to be contrasted from a background to be seen by a viewer, who may have a mental representation of the figure (i.e. knows what the figure features look like). Applying this framework to cancer, three players emerge: the viewer (immune system components), the figure (tumour), and the background (e.g., normal cells) with their dynamic interactions. Various characteristics of tumour development such as reduced expression of major-histocompatilibity complex (MHC) molecules or infiltration by inflammatory cells in its boundaries make tumour-immunity interplay highly suitable to an FG perspective. We describe the basic FG frame-work and immuno-biology of tumour development, thereafter reframed by the FG freamework. The term 'antigenic contrast' is introduced to reflect the contrast between the tumour figure and its variable background. Antigenic contrast emerges as a main factor enabling the immune system viewer to detect and mount adequate reactions against a tumour figure. We provide empirical examples of immunotherapeutic interventions whose results are explained by the FG perspective. For example, vaccines are forms of sharpening the 'mental' representation of the immune viewer concerning the tumour figure, while administering interferons can be seen as enhancing tumour figure salience by rescuing MHC expression. This framework highlights important elements in complex networks (e.g., cancer immunobiology), enhances communication between cancer scientists and clinicians, explains experimental and clinical study results, and provides further rationale for combinational immunotherapies.