{
  "abstract": "Background Transfer RNA-derived small RNAs (tsRNAs) have been implicated in tumor progression and immune regulation in recent years. However, the specific role of tRNA halves (tiRNAs), a subclass of tsRNAs, in modulating immunotherapy response remains unexplored. Methods and results In this study, 5’-tiRNAGly levels were examined in gastric cancer (GC) patients and found to be upregulated, especially in non-responders to anti-PD-1 therapy. Elevated 5’-tiRNAGly levels were also associated with diminished oxoglutarate dehydrogenase-like (OGDHL) expression. Further exploration revealed that 5’-tiRNAGly bound to DLST and promoted OGDHL destabilization, whereas targeted inhibition of 5’-tiRNAGly restored OGDHL stability through succinylation at lysine 910, enhanced tricarboxylic acid (TCA) cycle activity, and reduced glutamine-derived metabolic reprogramming. Additionally, 5’-tiRNAGly was found to decrease the activity of α-ketoglutarate dehydrogenase and inhibit succinylation of histone H3 at lysine 79 (H3K79suc), thereby downregulating PD-L1 transcription and reducing therapeutic responsiveness to PD-1 inhibitors. Conversely, restoration of this epigenetic modification upon 5’-tiRNAGly inhibition facilitated PD-L1 transcription, thereby sensitizing tumors to anti-PD-1 therapy. Conclusion Our findings indicate that targeting 5’-tiRNAGly may represent a promising strategy to enhance responsiveness to anti-PD-1 therapy in GC patients. Graphical Abstract Inhibition of 5’-tiRNAGly restores anti-PD-1 immunotherapy efficacy via DLST-mediated OGDHL succinylation in gastric cancer",
  "abstract_shown": true,
  "affiliations": [
    "Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University",
    "Department of Pharmacy, Affiliated Hospital of Nantong University, Pharmacy School of Nantong University",
    "Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University",
    "Department of Hematology, Affiliated Hospital of Nantong University, Medical School of Nantong University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xinliang Gu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xun Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuening Sun"
    },
    {
      "affs": [
        2
      ],
      "name": "Shuo Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyue Qin"
    },
    {
      "affs": [
        3
      ],
      "name": "Yuejiao Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xianjuan Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ming Zheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Quanhua Yi"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhiyuan Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaoqing Ju"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1nbxhrejpn2gp.bib",
  "cited_by": 0,
  "doi": "10.1186/s13046-026-03758-8",
  "fulltext_url": "https://doi.org/10.1186/s13046-026-03758-8",
  "id": "1nbxhrejpn2gp",
  "issns": [
    "1756-9966"
  ],
  "landing_url": "https://doi.org/10.1186/s13046-026-03758-8",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "1312|RNA modifications and cancer"
    ]
  ],
  "openalex": "W7164525754",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/1nbxhrejpn2gp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:38Z",
      "native_id": "e9f98d2f0a0f4c5d9521c3c110b673e5",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s13046-026-03758-8"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA modifications and cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Inhibition of 5’-tiRNAGly restores anti-PD-1 immunotherapy efficacy via DLST-mediated OGDHL succinylation in gastric cancer",
  "title_text": "Inhibition of 5’-tiRNAGly restores anti-PD-1 immunotherapy efficacy via DLST-mediated OGDHL succinylation in gastric cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:38Z",
  "url": "https://research.draconitic.com/paper/1nbxhrejpn2gp",
  "venue": "Journal of Experimental & Clinical Cancer Research",
  "versions": []
}