Activation of NOD1 on tumor-associated macrophages augments CD8⁺ T cell-mediated antitumor immunity in hepatocellular carcinoma.

ABSTRACT: The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway in hepatocellular carcinoma (HCC) is limited. NOD-like receptors (NLRs) comprise a highly evolutionarily conserved family of cytosolic bacterial sensors, yet their impact on antitumor immunity against HCC remains unclear. In this study, we uncovered that NOD1, a well-studied member of NLR family, exhibits predominant expression in tumor-associated macrophages (TAMs) and correlates positively with improved prognosis and responses to anti-PD-1 treatments in patients with HCC. Activation of NOD1 in vivo augments antitumor immunity and enhances the effectiveness of anti-PD-1 therapy. Mechanistically, NOD1 activation resulted in diminished expression of perilipin 5, thereby hindering fatty acid oxidation and inducing free fatty acid

SUBMITTER: Zhang F 

PROVIDER: S-EPMC11446285 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature