The role of TLR2 Activation in Promoting Tumor Dendritic Cell Dysfunction

Abstract

Dendritic cell (DC) dysfunction in cancer is a well-established phenomenon that is considered one of the main mechanisms of immune evasion. Defects in dendritic cells are caused primarily by tumor-derived factors present in the tumor microenvironment. However, the mechanisms that drive this process remain elusive. In our recent investigations, we reported that tumor-derived versican induces DC dysfunction through TLR2 activation. Ligation of TLR2 by tumor-derived factors sensitizes DCs to IL-6 and IL-10 by increasing their respective cytokine cell surface receptors expression, thus lowering the threshold of STAT3 activation. This mechanism reprograms sensitized DCs into immunosuppressive IL-10 producing cells. Our work revealed key molecular mechanisms of DC dysfunction in cancer and identified TLR2 as a relevant therapeutic target to improve DC immunogenicity and cancer immunotherapy.