Harnessing the immune system to fight cancer with Toll-like receptor and RIG-I-like receptor agonists

Cancer immunotherapy has come of age with the advent of immune checkpoint inhibitors. In this article we review how agonists for receptors of the innate immune system, the Toll-like receptors and the RIG-I-like receptors, impact anticancer immune responses. Treatment with these agonists enhances the activity of anticancer effector cells, such as cytotoxic T cells and NK cells, and at the same time blocks the activity of immunosuppressive cell types such as regulatory T cells and myeloid-derived suppressor cells. These compounds also impact the recruitment of immune cells to the tumor. The phenomena of pattern-recognition receptor tolerance and reprogramming and their implications for immunotherapy are discussed. Finally, novel delivery systems that target the immune-stimulating drugs to the tumor or the tumor-draining lymph nodes to enhance their efficacy and safety are presented.