{
  "abstract": "Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematologic malignancies but remain less efficacious in solid tumors. While PD-L1 blockade is widely used to counter tumor immune evasion, its direct effects on activated T cells, which also express PD-L1 and may engage in PD-L1/CD80 cis-interactions, remain largely unexplored. To investigate this, we blocked PD-L1 by engineering CAR T cells that secrete PD-L1-blocking single-chain variable fragment (scFv) antibodies derived from atezolizumab. Secretion of the scFv conferred no benefit: 4-1BB-based CAR T cells accumulated less upon repeated antigen stimulation, and CD28-based CAR T cells killed less efficiently when effector cells were limiting. Mechanistically, PD-L1 and CD80 form a cis-heterodimer on T cells that is disrupted by PD-L1 blockade, rendering CD80 susceptible to CTLA-4-mediated depletion and impairing CD28 co-stimulation. Consistent with this model, exogenous atezolizumab reduced CD80 expression and T cell viability, while CTLA-4 blockade with ipilimumab restored CD80 levels and rescued survival. These findings were corroborated by structural modeling demonstrating that atezolizumab disrupts the PD-L1/CD80 complex, and were reproduced in unmodified T cells and across both CD28- and 4-1BB-based CARs. Together, our findings uncover a T cell-intrinsic vulnerability to PD-L1 inhibitors that warrants consideration when PD-L1 blockade is combined with adoptive T cell therapy.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Sin-Syue Li"
    },
    {
      "name": "Markus Barden"
    },
    {
      "name": "Hong Pan"
    },
    {
      "name": "Dennis Christoph Harrer"
    },
    {
      "name": "Marcell Kaljanac"
    },
    {
      "name": "Valerie Bezler"
    },
    {
      "name": "Moritz Ertelt"
    },
    {
      "name": "Clara Schoeder"
    },
    {
      "name": "Tsai-Yun Chen"
    },
    {
      "name": "Hinrich Abken"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bcwd5ysm7fsay.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1906848",
  "fulltext_url": null,
  "id": "bcwd5ysm7fsay",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1906848",
  "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": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bcwd5ysm7fsay.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:20:45Z",
      "native_id": "10.3389/fimmu.2026.1906848",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1906848"
    },
    {
      "first_seen": "2026-11-02T12:23:23Z",
      "native_id": "10.3389/fimmu.2026.1906848",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1906848/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Anti-PD-L1 antibody limits the survival of activated CAR T cells by disrupting the PD-L1/CD80 cis-heterodimer",
  "title_text": "Anti-PD-L1 antibody limits the survival of activated CAR T cells by disrupting the PD-L1/CD80 cis-heterodimer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T00:25:32Z",
  "url": "https://research.draconitic.com/paper/bcwd5ysm7fsay",
  "venue": "Frontiers in Immunology",
  "versions": []
}