Toll-like receptors (TLRs) are a class of important protein molecules involved in the innate immune response, acting as a bridge between innate and adaptive immunity. TLRs recognize Pathogen-Associated Molecular Patterns (PAMPs) and trigger complex cascades of immune responses in the body, playing key roles in inflammation, immune cell regulation, and proliferation.
TLRs belong to the Type I transmembrane glycoprotein family and consist of three main domains: the extracellular domain, single transmembrane domain, and intracellular TLR domain. Human TLR receptors are divided into 5 subfamilies: TLR2, TLR3, TLR4, TLR5, and TLR9. TLR2 subfamily includes TLR1, TLR2, TLR6, and TLR10; TLR9 subfamily comprises TLR7, TLR8, and TLR9; TLR3, TLR4, and TLR5 form separate subfamilies.
TLRs play a role in adaptive immunity by recognizing various pathogens. Activation of TLRs can induce antimicrobial defense systems, leading to the production of IL-1β, IL-6, TNF, and chemokines, thus regulating the balance between Th1 and Th2 responses in the body. They are widely expressed in the immune cell spectrum, promoting T cell responses against tumors. Therefore, TLR agonists are being developed for cancer immunotherapy.
Each TLR is involved in specific types of cancer development and treatment: TLR2 is associated with oral and gastrointestinal cancers; TLR3 is implicated in neuroblastoma, breast cancer, hepatocellular carcinoma, papillary thyroid carcinoma, nasopharyngeal carcinoma, and lung cancer; TLR4 plays a role in lung cancer, neuroblastoma, colorectal cancer, and thyroid cancer; TLR9 shows varying levels of expression in prostate cancer, breast cancer, and astrocytoma patients' tumor samples. Reports also suggest that the expression of TLR9 and TLR5 gradually increases during the progression from low-grade cervical intraepithelial neoplasia (CIN) to high-grade CIN and then to invasive cervical squamous cell carcinoma.
Given the crucial role of TLRs in immune responses, they are becoming promising targets in the current wave of immunotherapy.
