Novel synthetic RORγ agonist compounds as a potential anti-tumor therapeutic approach

Selective enhancement (or activation) of the immune system by novel small molecules may be a potential therapeutic approach for the treatment of cancer. RORγt (Retinoic Acid Receptor-related orphan receptor) is the key transcription factor for the development of CD4+ Th17 cells, CD8+ Tc17 cells and IL-17+ innate immune cells including γδ T cells. A member of the nuclear receptor superfamily, RORγ modulates the expression of cytokines, chemokines and their receptors to induce a pro-inflammatory environment. RORγ can interact with other lineage-associated transcription factors resulting in developmental plasticity which reinforces immunity and limits immunosuppressive mechanisms. These activities suggest that the activation of RORγ may enhance anti-tumor immune responses and Th17 and Tc17 cells have been reported to have potent anti-tumor effects in vivo.