TLR4 Polymorphisms and Expression in Solid Cancers

Toll-like receptors (TLRs) are a type of pattern-recognition receptor (PRR) that are part of the innate immune system known to recognize pathogen-associated molecular patterns and thereby play a crucial role in host immune response. Among the various known TLRs, TLR4 is one of the most extensively studied PRRs expressed by immune, certain nonimmune, and tumor cells. When TLR4 binds with the bacterial lipopolysaccharide, it induces production of proinflammatory cytokines, chemokines, and effector molecules as part of the immune response. Continuous exposure to pathogens and TLR4 signaling results in chronic inflammation that may further lead to malignant transformation. TLR4 is a highly polymorphic gene, and genetic variations are known to influence host immune response, leading to dysregulation of signaling pathway, which may affect an individual's susceptibility to various diseases, including cancer. Furthermore, TLR4 expression in different tumor types may also serve as a marker for tumor proliferation, differentiation, metastasis, prognosis, and patient survival. This review aims to summarize various reports related to TLR4 polymorphisms and expression patterns and their influences on different cancer types with a special focus on solid tumors.