Fig. 1
From: Hedgehog/GLI signaling in tumor immunity - new therapeutic opportunities and clinical implications
Mechanisms of immune modulation by HH/GLI signaling in cancer and inflammation. 1) Cancer cells release CCL2/3 in response to oncogenic HH/GLI signaling, thereby recruiting TAMs and immunosuppressive MDSCs. 2) HH/GLI-induced PD-L1 expression in cancer and dendritic cells inhibits tumor specific cytotoxic T-cells via binding to PD-1. 3) GLI2 drives production of immunosuppressive cytokines and growth factors (IL10 and TGFβ), which results in the inactivation of tumor specific CD8+ T-cells. 4) HH/GLI-induced IL10 from stromal cells promotes FoxP3 expression in regulatory T-cells. 5) Pro-inflammatory signals such as IL6/STAT3 interact with HH/GLI signaling; HH/GLI-induced autocrine IL6 signaling and/or pro-inflammatory IL6 from TAM and stromal cells activate STAT3 signaling in cancer cells, thereby promoting malignant growth