Photodynamic therapy combined with immunotherapy effectively improved malignant gastric outlet obstruction in“immune-desert”gastric cancer by regulating tumor immune microenvironment and gut flora

Current therapies for malignant gastric outlet obstruction (MGOO), such as stent insertion alleviate obstruction temporarily, without affecting tumor cells. Photodynamic therapy (PDT), known for rapid tumor reduction and fewer side effects, lacksa valid validationin MGOO. This study assessed efficacy, safety, and mechanisms of PDT in MGOO management. Analyzed were 49 MGOO patients pathologically confirmed to be immune desert-type gastric cancer and treated with PDT +Stent (n=28) and Stent-only (n=21) (April 2020-November 2022). Comparison between two groups included survival outcomes, short/long-term effectiveness, and adverse reactions. Pre-/post-PDT peripheral blood, tissue samples were analyzed via flow cytometry, immunohistochemistry and transcriptome sequencing, and stool specimen for RNA/16S rRNA sequencing. The Stent+PDT group showed enhanced survival compared to Stent-only (median: 11 vs. 5 months, P=0.004). Postoperative GOOSS scores, KPS, and clinical stage were key prognosis predictors. Stent+PDT group attained 78.6% short-term disease control, improved GOOSS/KPS scores (P<0.001), and better long-term tumor reduction (mean: -5.91 mm, P=0.049) than Stent-only. PDT showed no significant adverse reactions. Post-PDT, systemic immune function and M1 macrophage diversity increased. Gene expression analysis revealed 6, 406 differentially expressed genes in diverse signaling pathways. Fecal analysis showed increased Bifidobacteria post-PDT (P<0.05). PDT plus stenting safely improves MGOO by modulating the immune microenvironment, gene expression, and gut flora.