Mannose Inhibits NSCLC Growth and Inflammatory Microenvironment by Regulating Gut Microbiota and Targeting OGT/hnRNP...

Area of Science:

• Oncology
• Immunology
• Metabolomics

Background:

• Mannose, a monosaccharide, has demonstrated direct antitumor effects.
• The impact of mannose on non-small cell lung cancer (NSCLC) and its inflammatory microenvironment requires further investigation.

Purpose of the Study:

• To investigate the regulatory effects of mannose on NSCLC growth and the inflammatory microenvironment.
• To explore mannose's potential to enhance immune checkpoint inhibitor efficacy.
• To elucidate the molecular mechanisms underlying mannose's action in NSCLC.

Main Methods:

• Utilized cancer cell lines, animal models, organoids, and multi-omics approaches.
• Conducted in vitro and in vivo experiments to assess mannose's effects.
• Analyzed changes in gut microbiota, blood, and fecal metabolites.

Main Results:

• Mannose inhibited NSCLC cell growth, inflammatory cell infiltration, and cytokine expression.
• Mannose enhanced the antitumor efficacy of immune checkpoint inhibitors.
• Oral mannose administration modulated gut microbiota and increased beneficial metabolites.
• Mannose suppressed JUN mRNA stability and IL-8 transcription by targeting OGT and hnRNP R glycosylation.

Conclusions:

• Mannose suppresses NSCLC by inhibiting tumor growth and the inflammatory microenvironment.
• Mannose demonstrates potential as an adjunct therapy for NSCLC.
• The study reveals a novel molecular mechanism involving O-GlcNAc glycosylation in mannose's antitumor activity.