Toll-like receptor-targeted particles: A paradigm to manipulate the tumor microenvironment for cancer immunotherapy

Abstract

The expression of Toll-like receptors (TLRs) on antigen presenting cells, especially dendritic cells, offers several sensitive mediators to trigger an adaptive immune response, which potentially can be exploited to detect and eliminate pathogenic objects. Consequently, numerous agonists that target TLRs are being used clinically either alone or in combination with other therapies to strengthen the immune system in the battle against cancer. This review summarizes the roles of TLRs in tumor biology, and focuses on relevant TLR-dependent antitumor pathways and the conjugation of TLR agonists as adjuvants to nano- and micro-particles for boosting responses leading to cancer suppression and eradication. STATEMENT OF SIGNIFICANCE: Toll-like receptors (TLRs), which express on antigen presenting cells, such as dendritic cells and macrophages, play an important role in sensing pathogenic agents and inducing adaptive immunity. As a result, several TLR agonists have been investigating as therapeutic agents individually or in combination with other treatment modalities for cancer treatment through boosting the immune system. This review aims to focus on the roles of TLRs in cancer and TLR-dependent antitumor pathways as well as the use of different nano- or micro-particles bearing TLR agonists for tumor inhibition and elimination.

Keywords: Biomaterials; Cancer; Immunotherapy; Particulate systems; Toll-like receptors.