The interplay between pathogen-associated and danger-associated molecular patterns: an inflammatory code in cancer?

There is increasing evidence of a close link between inflammation and cancer, and at the core of inflammation there are both pathogen-associated molecular patterns (PAMPs) and danger (or damage)-associated molecular patterns (DAMPs). Microorganisms harbor molecules structurally conserved within groups called PAMPs that are recognized by specific receptors present on immune cells, such as monocytes and dendritic cells (DCs); these are the pattern recognition receptors (PRRs). Activation through different PRRs leads to production of pro-inflammatory cytokines. A robust immune response also requires the presence of endogenous molecules that pose 'danger' to self-tissues and are produced by damaged or stressed cells; these are the DAMPs, which act also as inducers of inflammation. PAMPs and DAMPs are each recognized by a limited set of receptors that in number probably do not exceed 100. PAMPs and DAMPs interact with each other, and a single PRR can bind to a PAMP as well as a DAMP. Within this framework, we propose that PAMPs and DAMPs act in synchrony, modifying the activation threshold of one another. Thus, the range of PAMP-DAMP partnerships defines the course of inflammation, in a predictable manner, in an 'inflammatory code'. The definition of relevant PAMP-DAMP complexes is important for the understanding of inflammatory disorders in general, and of cancer in particular. Here, we review relevant findings that support the notion of a PAMP-DAMP-based inflammatory code, with emphasis on cancer immunology and immunotherapy.