{
  "abstract": "CD8 ⁺ T cells play a crucial role in anti-tumor immunity; however, their functionality is compromised by exhaustion driven by chronic antigen exposure, poor tumor microenvironment, and metabolic dysfunction. Activated CD8 ⁺ T cells undergo extensive proteomic remodeling, which includes the induction of the IRE1-XBP1 signaling axis of the unfolded protein response. However, the functional consequences of sustained IRE1-XBP1 activation in exhausted CD8 ⁺ T cells remain elusive. Using a model of constitutive XBP1 activation in CD8 ⁺ T cells, we demonstrate that sustained XBP1s signaling leads to reduced homeostatic CD8 ⁺ T cell populations, impaired migratory capacity, and dampened anti-tumor immunity. Notably, pharmacological inhibition of the IRE1-XBP1 axis significantly reduces tumor burden through a dual mechanism that targets both tumor cells and the immune compartment. Our findings reveal a previously unappreciated role for XBP1s in regulating CD8 ⁺ T cell biology and highlight the IRE1-XBP1 axis as a therapeutic target in solid tumors.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center , , ,",
    "Houston Methodist Neal Cancer Center, Houston Methodist Research Institute , , ,",
    "The Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Keith Alan Nair"
    },
    {
      "affs": [
        0
      ],
      "name": "Jessica Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Olivia Zaleski"
    },
    {
      "affs": [
        0
      ],
      "name": "Luciano Mazzoccoli"
    },
    {
      "affs": [
        0
      ],
      "name": "Brian Deng"
    },
    {
      "affs": [
        1
      ],
      "name": "Chih-Chi Andrew Hu"
    },
    {
      "affs": [
        2
      ],
      "name": "Stanley Ching-Cheng Huang"
    },
    {
      "affs": [
        2
      ],
      "name": "Andreas Wieland"
    },
    {
      "affs": [
        2
      ],
      "name": "Hazem E. Ghoneim"
    },
    {
      "affs": [
        2
      ],
      "name": "Haitao Wen"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaopei Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Bei Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2cb6dz4srn9ka.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1940201",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672639/?tool=EBI",
  "id": "2cb6dz4srn9ka",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13672639",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1307|Endoplasmic Reticulum Stress and Disease"
    ]
  ],
  "openalex": "W7215924148",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672639/pdf/?tool=EBI",
  "pmcid": "PMC13672639",
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2cb6dz4srn9ka.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13672639",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13672639"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1940201",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940201/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Endoplasmic Reticulum Stress and Disease",
      "subfield": "cell-biology"
    }
  ],
  "title": "Chronic XBP1s-mediated activation of the unfolded protein response impairs CD8+ T cell anti-tumor immunity",
  "title_text": "Chronic XBP1s-mediated activation of the unfolded protein response impairs CD8+ T cell anti-tumor immunity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/2cb6dz4srn9ka",
  "venue": "Frontiers in immunology",
  "versions": []
}