{
  "abstract": "Immune checkpoint blockade restores antitumor T cell responses, but efficacy can be limited by insufficient costimulation. Here, we investigated CD226 agonism and generated a CD226×PD-L1 bispecific Ab combining CD226 costimulation with PD-L1 blockade. CD226 agonism enhanced responses to limiting TCR stimulation and IL-2-driven responses in the absence of concurrent TCR stimulation. The bispecific Ab elicited stronger CD4+ and CD8+ T cell responses than either Ab alone or the combination. Conditioning CD226 agonism on target cell PD-L1 engagement produced greater T cell and NK cell cytotoxicity than the combination, particularly under effector-limited conditions and repeated target challenges. It also improved tumor control in adoptive-transfer models using antigen-specific TCR-T cells and remained effective with preactivated T cells despite the absence of continued cognate antigen stimulation. These findings identify PD-L1-directed CD226 agonism as a potential immunotherapeutic strategy that exploits the signal-amplifying properties of CD226 to reinforce antitumor lymphocyte responses under limiting stimulation.",
  "abstract_shown": true,
  "affiliations": [
    "Chemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea .",
    "Department of Life Sciences, Korea University, Seoul 02481, Korea .",
    "Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea .",
    "National Research Laboratory for Convergence Degradation Biology, Korea University, Seoul 02481, Korea .",
    "Division of Biomedical Science and Technology, Korea Institute of Science and Technology (KIST) School, University of Science and Technology (UST), Seoul 02792, Korea ."
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yunju Jo",
      "orcid": "0000-0002-7038-7832"
    },
    {
      "affs": [
        2
      ],
      "name": "Hyejin Ahn",
      "orcid": "0009-0003-9886-7322"
    },
    {
      "affs": [
        2
      ],
      "name": "Hye-Bin Kim",
      "orcid": "0000-0001-9773-3144"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Gaeun Song",
      "orcid": "0009-0004-3065-8986"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hye-In Sim",
      "orcid": "0009-0001-3548-6536"
    },
    {
      "affs": [
        2
      ],
      "name": "Kiyeon Park",
      "orcid": "0009-0005-4476-8382"
    },
    {
      "affs": [
        2
      ],
      "name": "Taehyeong Kim",
      "orcid": "0009-0004-4848-3336"
    },
    {
      "affs": [
        2
      ],
      "name": "Haeun Son",
      "orcid": "0009-0009-3470-4077"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Hyun Kyu Song",
      "orcid": "0000-0001-5684-4059"
    },
    {
      "affs": [
        2
      ],
      "name": "Hyung-seung Jin",
      "orcid": "0000-0002-3186-3488"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Yoon Park",
      "orcid": "0000-0002-0871-8901"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/77xbeghsjn839.bib",
  "cited_by": 0,
  "doi": "10.4110/in.2026.26.e46",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13744920/",
  "id": "77xbeghsjn839",
  "issns": [
    "1598-2629",
    "2092-6685"
  ],
  "landing_url": "https://doi.org/10.4110/in.2026.26.e46",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Brief Communication"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7224122190",
  "pdf_url": null,
  "pmcid": "PMC13744920",
  "pmid": "43001293",
  "published": "2026-10-16",
  "publisher": "The Korean Association of Immunologists",
  "ris": "https://research.draconitic.com/paper/77xbeghsjn839.ris",
  "sources": [
    {
      "first_seen": "2026-11-11T12:22:22Z",
      "native_id": "PMC13744920",
      "source": "pmc",
      "url": "https://doi.org/10.4110/in.2026.26.e46"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "PD-L1-Directed CD226 Agonism Enhances Antitumor Activity by Amplifying T Cell Responses to Limiting Stimulation",
  "title_text": "PD-L1-Directed CD226 Agonism Enhances Antitumor Activity by Amplifying T Cell Responses to Limiting Stimulation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-12T12:21:19Z",
  "url": "https://research.draconitic.com/paper/77xbeghsjn839",
  "venue": "Immune Network",
  "versions": []
}