Exploring the modulation of TLR4 and its associated ncRNAs in cancer immunopathogenesis, with an emphasis on the therapeutic implications and mechanisms underlying drug resistance

Hum Immunol. 2024 Dec 3;86(1):111188. doi: 10.1016/j.humimm.2024.111188. Online ahead of print.

Abstract

This study provides an in-depth analysis of the pathogenic relevance, therapeutic implications, and mechanisms of treatment resistance associated with TLR4 and its ncRNAs in cancer immunopathogenesis. TLR4, a pivotal component of the innate immune response, has been implicated in promoting inflammation, tumorigenesis, and immune evasion across various malignancies, including gastric, ovarian, and hepatocellular carcinoma. The interactions between TLR4 and specific ncRNAs, such as lncRNAs and miRNAs, play a crucial role in modulating TLR4 signaling pathways, influencing immune cell dynamics, and contributing to chemoresistance. These ncRNAs facilitate tumor-promoting processes, including macrophage polarization, dendritic cell suppression, and T-cell regulation, effectively establishing an immunosuppressive tumor microenvironment that further enhances therapeutic resistance. A comprehensive understanding of the complex interplay between TLR4 and ncRNAs unveils potential avenues for identifying predictive biomarkers and discovering novel therapeutic targets in cancer. Future research initiatives should prioritize the development of personalized therapeutic strategies that specifically target TLR4 signaling and its ncRNA regulators to counteract drug resistance and improve clinical outcomes. This review extensively evaluates the role of TLR4 in cancer biology, emphasizing its critical importance in developing innovative cancer management strategies.

Keywords: Cancer; Drug resistance; Pathogenesis; TLR4; Treatment; ncRNAs.

Publication types

  • Review