Microbial-Derived Toll-like Receptor Agonism in Cancer Treatment and Progression

SIMPLE SUMMARY: Toll like receptors (TLRs) are a group of transmembrane receptors belonging to the class of pattern recognition receptors (PRR), which are involved in recognition of pathogen associated molecular patterns (PAMPs), inducing immune response. During the past decade, a number of preclinical and clinical breakthroughs in the field of TLR agonists has immerged in cancer research and some of these agents have performed exceptionally well in clinical trials. Based on evidence from scientific studies, we draw attention to several microbial based TLR agonists and discuss their relevance in various cancer and explore various microbial based TLR agonists for developing effective immunotherapeutic strategies against cancer. ABSTRACT: Toll-like receptors (TLRs) are typical transmembrane proteins, which are essential pattern recognition receptors in mediating the effects of innate immunity. TLRs recognize structurally conserved molecules derived from microbes and damage-associated molecular pattern molecules that play an important role in inflammation. Since the first discovery of the Toll receptor by the team of J. Hoffmann in 1996, in Drosophila melanogaster, numerous TLRs have been identified across a wide range of invertebrate and vertebrate species. TLR stimulation leads to NF-κB activation and the subsequent production of pro-inflammatory cytokines and chemokines, growth factors and anti-apoptotic proteins. The expression of TLRs has also been observed in many tumors, and their stimulation results in tumor progression or regression, depending on the TLR and tumor type. The anti-tumoral effects can result from the activation of anti-tumoral immune responses and/or the direct induction of tumor cell death. The pro-tumoral effects may be due to inducing tumor cell survival and proliferation or by acting on suppressive or inflammatory immune cells in the tumor microenvironment. The aim of this review is to draw attention to the effects of TLR stimulation in cancer, the activation of various TLRs by microbes in different types of tumors, and, finally, the role of TLRs in anti-cancer immunity and tumor rejection.