Targeting Toll like Receptors in Cancer: Role of TLR Natural and Synthetic Modulators

Abstract

Background: Toll like receptors (TLRs) are a group of transmembrane receptors belonging to the broad class pattern recognition receptors (PRR), involved in the recognition of Pathogen Associated Molecular Patterns (PAMPs) and thereby inducing an immune response. Apart from these exogenous PAMPs, numerous endogenous PAMPs are also ligands for various TLRs thereby activating the TLR dependent immune response, subsequently leading to the onset of an inflammatory response. Prolonged activation of TLR by these endogenous PAMPs leads to chronic inflammatory insults to the body and which in turn alters the proliferative patterns of the cells, which ultimately leads to the development of cancer. Objectives: The present review aims to provide a detailed outline of the differential roles of various TLRs in cancer and the possible use of them as a therapeutic target. Methods: Data were collected from PubMed/Sciencedirect/Web of Science database and sorted; the latest literature on TLRs was incorporated in the review. Results: Among the different TLRs, few are reported to be anti-neoplastic, which controls the cell growth and multiplication in response to the endogenous signals. On the contrary, numerous studies have reported the pro-carcinogenic potentials of TLRs. Hence, TLRs has emerged as a potential target for the prevention and treatment of various types of cancers. Several molecules such as monoclonal antibodies, small molecule inhibitors and natural products have shown promising anticancer potential by effectively modulating the TLR signalling. Conclusion: Toll like receptors play vital roles in the process of carcinogenesis, hence TLR targeting is a promising approach for cancer prevention.

RNF115 Inhibits the Post‐ER Trafficking of TLRs and TLRs‐Mediated Immune Responses by Catalyzing K11‐Linked Ubiquitination of RAB1A and RAB13

“…TLRs play crucial roles in antimicrobial immunity, autoimmunity, tumorigenesis, and tumor metastasis. [ 16,64,65 ] We found that RNF115 negatively regulated TLRs‐mediated autoimmunity and antimicrobial immunity. While accumulating evidence shows that RNF115 promotes cancer development and indicates RNF115 as a therapeutic target for cancer, [ 30,42 ] the identification of RNF115 as an inhibitor of the trafficking and the activation of TLRs raises the caution for autoimmunity when targeting RNF115 for cancer treatment.…”

C chemokines are prognostic biomarkers correlated with diverse immune cell infiltrations in clear cell renal cell carcinoma

“…Accumulating evidence has confirmed the pro-metastatic effect of the XCL1/XCR1 axis (36)(37)(38). Moreover, many studies have focused on applying small-molecule modulators targeting TLRs for cancer treatment (42,43). For example, the combination of immune modulatory oligonucleotide, an agonist of TLR9, and everolimus synergistically inhibited the growth and angiogenesis of RCC (44).…”

The Role of Cytokines and Pattern Recognition Receptors in Inflammation Caused by Helicobacter pylori Infection in Gastric Cancer

“…81 On the other hand, TLRs are a group of membrane receptors belonging to PRRs that are involved in identifying PAMPs, thereby causing an immune response. 82 The TLRs are the first line of defense against pathogens. 38 Therefore, targeting TLR and pathogenic factors of H. pylori to induce apoptosis and stimulate the immune system will be a promising, attractive, and helpful method for cancer prevention.…”