TLR4 exhibits a Pivotal Role in Immuno-Oncology through Systematic
Pan-Cancer Analysis
Abstract
The role of TLR4 (toll like receptor 4), a key molecule of the classical
innate immune pathway, in individual tumors requires further
exploration. In this study, numerous databases and tools, such as TCGA,
GTEx, cBioportal, GSCALite, and GDSC, were utilized to systematically
analyze the prognostic and immunological potential of TLR4 in tumors.
The expression levels and mutational dynamics of TLR4 in pan-cancer were
investigated. The prognostic potential of TLR4 was analyzed using
Kaplan-Meier (KM) analysis. Results showed the levels of TLR4 in tumor
tissues were significantly lower as compared to those in normal tissues
in most cancers and were strongly correlated with the patient’s
outcomes. The mutant genes associated with TLR4 were mainly enriched in
the PI3K-AKT pathway. This could be a potential pathway for radiotherapy
to activate the tumor immune microenvironment via TLR4/MAP. In tumors,
the TLR4 mutations were closely associated with the M1/M2 polarization
of macrophages. TLR4 and its ligand CD14 were significantly negatively
associated with immunosuppressed MDSCs and TAM M2. The intervention of
TLR4-dependent signaling pathways might be a promising strategy to
reduce tolerance to ICB treatment in the post-immune era. In conclusion,
this study expands the potential of TLR4 as an immune target in tumor
therapy.