biostudies-literatureUnknown13(9)Sun S<h4>Background</h4>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.<h4>Methods</h4>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 <i>Akkermansia muciniphila</i> (<i>AKK</i>) on 5-HIAA synthesis, antitumor immunity and immunotherapy efficacy were analyzed. Finally, the synergistic effect of Phe combined with <i>AKK</i> on antiJournal for immunotherapy of cancere011831https://www.ebi.ac.uk/biostudies/studies/S-EPMC12421609biostudies-literatureEnhancing immunotherapy efficacy in NSCLC through the combined use of phenelzine and &lt;i&gt;Akkermansia muciniphila&lt;/i&gt; to regulate gut microbial metabolite 5-HIAA.PMC12421609Zheng YCui KLi CChao KYu PWei YLi LWang LDing YShen ZYang YJi WZhu LZhang YGe YSun SSethi GZhao JSong YfalseEnhancing immunotherapy efficacy in NSCLC through the combined use of phenelzine and &lt;i&gt;Akkermansia muciniphila&lt;/i&gt; to regulate gut microbial metabolite 5-HIAA.<h4>Background</h4>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.<h4>Methods</h4>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 <i>Akkermansia muciniphila</i> (<i>AKK</i>) on 5-HIAA synthesis, antitumor immunity and immunotherapy efficacy were analyzed. Finally, the synergistic effect of Phe combined with <i>AKK</i> on anti2025-01-01T00:00:00Z2025 Sep2026-06-02T20:24:05.396Z2026-04-20T03:09:58.743ZS-EPMC124216094093074810.1136/jitc-2025-011831