Prophylactic and therapeutic implications of toll‐like receptor ligands

Abstract

The evolutionary conserved Toll-like receptors (TLRs) are the first identified and best characterized pattern recognition receptors (PRRs) which discriminate self from nonself, providing an early and effective immune response against invading pathogens. The ever expanding knowledge of TLR signaling network make it one of the most promising therapeutic strategies to modulate the immune response in various human diseases. Immune modulating strategies based on TLR-specific agonists elicit a potent immune response to adjuvant vaccine immunotherapy, cancers, allergic diseases, and chronic viral infections while minimizing the risk of uncontrolled provocation of systemic inflammatory response. Moreover, the contribution of TLR signaling in the pathogenesis of chronic noninfectious inflammatory and autoimmune diseases provides the rationale for the development and clinical implementation of TLR-specific antagonists. At present, a few TLR-specific agonists have been approved for both prophylactic and therapeutic applications, while the ongoing preclinical and clinical studies show promising results on various novel therapeutic molecules as an adjunctive to conventional pharmacotherapy or stand-alone therapeutic strategy.

Intraperitoneal Oxidative Stress in Rabbits with Papillomavirus-Associated Head and Neck Cancer Induces Tumoricidal Immune Response That Is Adoptively Transferable

“…Damage-associated molecular pattern molecules (DAMP refs. 27, 28) such as DNA/RNA fragments, glucose, or ATP released from VX2 tumor cells by itself or from cells of the TME might function as ligands for these PRRs (29). In fact, DAMPs are often critical for tumor development.…”

Experimental immunology Determination of mRNA three Toll-like receptors in human carcinoma cell lines

“…On the other hand, it has been shown by some of us that TLR-4 promotes tumor growth in a head and neck cell line carcinoma model [12]. Nevertheless, there is growing interest in application of TLR ligands or agonists as therapeutic agents in pathological conditions and in particular, in malignancies [13,14].…”

Cancer and the microbiome: potential applications as new tumor biomarker

“…Recently, several Phase I and II clinical trials have been registered to examine the prophylactic and therapeutic potential of TLR agonists/antagonists in various cancers [112]. For example, in melanoma and basal-cell carcinoma patients, intra-tumor injection of PF-3512676 (a TLR agonist) was shown to be able to induce regression of skin lesions [113,114].…”