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

• Published in: Immunology and cell biology Vol. 91; no. 10; pp. 601 - 610
• Main Authors: Escamilla‐Tilch, Monica, Filio‐Rodríguez, Georgina, García‐Rocha, Rosario, Mancilla‐Herrera, Ismael, Mitchison, Nicholas Avrion, Ruiz‐Pacheco, Juan Alberto, Sánchez‐García, Francisco Javier, Sandoval‐Borrego, Daniela, Vázquez‐Sánchez, Ernesto Antonio
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-11-2013; Blackwell Science Ltd
• Subjects: Animals; cancer; DAMPs; Humans; Immunotherapy; Inflammation - immunology; inflammatory response; Neoplasms - immunology; Neoplasms - therapy; PAMPs; PRRs; Receptors, Pattern Recognition - metabolism
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1038/icb.2013.58

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.