Directing toll-like receptor signaling in macrophages to enhance tumor immunotherapy

A key challenge facing immunotherapy is poor infiltration of T cells into tumors, along with suppression of cells reaching these sites. However, macrophages make up a majority of immune cell infiltrates into tumors, creating natural targets for immunotherapies able to direct macrophages away from tumor-supportive functions and toward anti-tumor phenotypes. Recent studies demonstrate that toll-like receptors (TLRs) - pathways that quickly trigger early immune responses - play an important role in polarizing macrophages. Here, we present emerging ways in which TLR signaling is being manipulated in macrophages to create new opportunities for cancer immunotherapy. In particular, we discuss approaches to deliver TLR agonists, to leverage biomaterials in these therapies, and to couple TLR-based approaches with other frontline treatments as combination cancer therapies.