Targeting pattern recognition receptors in cancer immunotherapy.

Pattern recognition receptors (PRRs) are known for many years for their role in the recognition of microbial products and the subsequent activation of the immune system. The 2011 Nobel Prize for medicine indeed rewarded J. Hoffmann/B. Beutler and R. Steinman for their revolutionary findings concerning the activation of the immune system, thus stressing the significance of understanding the mechanisms of activation of the innate immunity. Such immunostimulatory activities are of major interest in the context of cancer to induce long-term antitumoral responses. Ligands for the toll-like receptors (TLRs), a well-known family of PRR, have been shown to have antitumoral activities in several cancers. Those ligands are now undergoing extensive clinical investigations both as immunostimulant molecules and as adjuvant along with vaccines. However, when considering the use of these ligands in tumor therapy, one shall consider the potential effect on the tumor cells themselves as well as on the entire organism. Recent data indeed demonstrate that TLR activation in tumor cells could trigger both pro- or antitumoral effect depending on the context. This review discusses this balance between the intrinsic activation of PRR in tumor cells and the extrinsic microenvironment activation in term of overall effect of PRR ligands on tumor development. We review recent advances in the field and underline appealing prospects for clinical development of PRR agonists in the light of our current knowledge on their expression and activation.