Wnt Signaling as a Master Regulator of Immune Tolerance in a Tumor Microenvironment

Aberrant Wnt signaling is a hallmark of many cancer types such as colon cancer. However, the effect of altered Wnt signaling is not only restricted to cancer cells but also dynami cally interacts with a tumor microenvironment and has the ability to directly regulate the anti-tumor immune response. It has been reported that tumors induce immune tolerance through the activation of canonical Wnt signaling in dendritic cells promoting T regula - tory responses, and also that both canonical and noncanonical Wnt proteins program dendritic cell responses for tolerance. Thus, the Wnt signaling pathway may be a novel and promising therapeutic target for anticancer immunotherapy. In this review, we will discuss the molecular mechanisms involved in immune cell response regulation medi - ated by canonical and noncanonical Wnt signaling. C (PLC) to produce diacylglycerol and Ca 2+ mobilization that activates PKC isoforms, other Ca 2+ -modulated kinases and calcineurin phosphatase, which in turn promotes NFAT translocation to the nucleus.