{
  "abstract": "Objective: To investigate whether the Jiangshui-derived probiotic Lactobacillus plantarum GR-4 can enhance gastric cancer sensitivity to PD-1 inhibitors and reshape the tumor immune microenvironment.\n\nMethods: A mouse gastric cancer model was established. Mice received oral GR-4 monotherapy, PD-1 blocking antibody monotherapy, or combined GR-4 and PD-1 antibody treatment. In vivo antitumor efficacy was evaluated by measuring tumor weight. We assessed CD8 ⁺ T-cell infiltration, cytokines related to T-cell activation and differentiation, and the expression of the activation marker CD69 on CD3 ⁺ /CD8 ⁺ T cells within tumor tissues. 16S rRNA sequencing of gut microbiota and fecal metabolomic analysis were performed to explore the regulatory effects of GR-4 on gut microbiota composition and metabolic profiles. In vitro , human gastric cancer BGC-823 cells were treated with GR-4 combined with PD-1 intervention, and transcriptome sequencing was applied to further validate the underlying molecular regulatory mechanisms.\n\nResults: In vivo results demonstrated that combined GR-4 and PD-1 antibody treatment exerted prominent synergistic antitumor activity, effectively suppressing tumor growth while markedly mitigating PD-1-associated body weight loss (p < 0.01). Further assays revealed that GR-4 synergistically elevated tumor-infiltrating CD3 ⁺ /CD8 ⁺ T-cell levels and upregulated CD69 expression on these cells, thereby remodelling the tumor immune microenvironment. Additionally, GR-4, whether administered alone or combined with PD-1 antibody, optimized gut microbiota structure, increased the abundance of probiotic genera including Ligilactobacillus and Bacteroides , reversed intestinal metabolic disturbances, and raised the levels of short-chain fatty-acid-related metabolites such as ethoxyacetic acid and 2,5-dihydroxybenzoic acid. Transcriptomic sequencing showed significant enrichment of the PD-1 checkpoint pathway in the GR-4 group versus Ctrl (p=0.01), whereas no significant enrichment was observed between the PD-1 inhibitor group and GR-4/PD-1 inhibitor group (p=0.14).\n\nConclusion: This study is the first to confirm that Lactobacillus plantarum GR-4 synergizes with PD-1 inhibitors to restrain gastric cancer progression via T-cell activation and elevated intratumoral T-cell infiltration. These findings provide novel theoretical evidence and a potential combinatorial immunotherapeutic strategy for gastric cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oncology, The Second Hospital & Clinical Medical School, Lanzhou University",
    "Departments of Orthopedics, The Second Hospital & Clinical Medical School, Lanzhou University",
    "Centre for Grassland Microbiome, State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, College of Pastoral Agricultural Science and Technology, Lanzhou University",
    "Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University",
    "The Second Hospital & Clinical Medical School, Lanzhou University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Na Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Kai Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Huawen Han"
    },
    {
      "affs": [
        3
      ],
      "name": "Jingwen Fan"
    },
    {
      "affs": [
        0
      ],
      "name": "Feixue Song"
    },
    {
      "affs": [
        4
      ],
      "name": "Hao Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiangkai Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8k72kceswnakf.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1987320",
  "fulltext_url": null,
  "id": "8k72kceswnakf",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1987320/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8k72kceswnakf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:19Z",
      "native_id": "10.3389/fimmu.2026.1987320",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1987320/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Jiangshui-derived Lactobacillus plantarum GR-4 enhances the therapeutic efficacy of PD-1/PD-L1 inhibitors against gastric cancer",
  "title_text": "Jiangshui-derived Lactobacillus plantarum GR-4 enhances the therapeutic efficacy of PD-1/PD-L1 inhibitors against gastric cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T00:20:59Z",
  "url": "https://research.draconitic.com/paper/8k72kceswnakf",
  "venue": "Frontiers in Immunology",
  "versions": []
}