Enhancing immunotherapy efficacy in NSCLC through the combined use of phenelzine and <i>Akkermansia muciniphila</i> to regulate gut microbial metabolite 5-HIAA.

ABSTRACT:

Background

Improving the efficacy of anti-programmed death 1 (PD-1) monoclonal antibody (mAb) therapy remains a major challenge for cancer immunotherapy in non-small cell lung cancer (NSCLC). Gut microbial metabolites can influence immunotherapy efficacy.

Methods

ELISA was used to compare the serum 5-hydroxyindoleacetic acid (5-HIAA) level in patients with NSCLC. Humanized mice were constructed to observe the effect of 5-HIAA on immunotherapy. RNA-seq and flow cytometry were used to analyze the effect of 5-HIAA on tumor-infiltrating lymphocytes. The effects of phenelzine (Phe) and Akkermansia muciniphila (AKK) on 5-HIAA synthesis, antitumor immunity and immunotherapy efficacy were analyzed. Finally, the synergistic effect of Phe combined with AKK on anti

SUBMITTER: Sun S 

PROVIDER: S-EPMC12421609 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature