{
  "abstract": "Folate is a driver of one-carbon metabolism that is essential in T cells. The cellular consequences of its deprivation in CD8+ T cells and impact on anti-tumor function are unknown. Single cell RNA-seq analysis of primary central nervous system lymphoma (PCNSL) patients' tumor samples revealed exhaustion in T cells with high folate metabolism gene expression signature. Functional genomics, metabolite profiling, and glycomics identified disrupted cell surface glycosylation as a major consequence of folate deprivation in CD8+ T cells. Mechanistically, folate deprivation reduced nucleotide sugar levels, perturbed glycosylation, and triggered the apoptotic unfolded protein response. Overexpressing folate transporters in adoptively transferred CD8+ T cells increased intratumoral T cell numbers and reduced exhaustion. Therefore, our data draw a mechanistic line between one-carbon metabolism, cell-surface glycosylation, and anti-tumor T cell function, and support a hypothesis that increased folate uptake can enhance CD8+ T cell function including ex vivo and in vivo CAR-T cells.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Boston Children's Hospital, Boston, MA, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "name": "P. Wang"
    },
    {
      "name": "A. Yu"
    },
    {
      "name": "M. Mutaher"
    },
    {
      "name": "A. S. Eisele"
    },
    {
      "name": "S. Mouche"
    },
    {
      "name": "K. Hung"
    },
    {
      "name": "R. Larson"
    },
    {
      "name": "M. Gish"
    },
    {
      "name": "M. Zimmer"
    },
    {
      "name": "J. R. Brook"
    },
    {
      "name": "M. McNerney"
    },
    {
      "name": "L. Hammer"
    },
    {
      "name": "A. Garg"
    },
    {
      "name": "E. Ozeri"
    },
    {
      "name": "A. Y. Wong"
    },
    {
      "name": "B. Petrova"
    },
    {
      "name": "M. Weitman"
    },
    {
      "name": "R. C. Sun"
    },
    {
      "name": "M. Schwartz"
    },
    {
      "name": "J. Tamburini"
    },
    {
      "name": "M. Wenes"
    },
    {
      "name": "N. Hacohen"
    },
    {
      "affs": [
        0
      ],
      "name": "N. Kanarek"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5wqcv8ty9xqts.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.06.756889",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756889v1.full",
  "id": "5wqcv8ty9xqts",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756889v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2745|Folate and B Vitamins Research"
    ]
  ],
  "openalex": "W7220864481",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756889v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5wqcv8ty9xqts.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:25Z",
      "native_id": "10.64898/2026.10.06.756889",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756889v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "One-carbon metabolism sustains effector T cell function through cell-surface glycosylation",
  "title_text": "One-carbon metabolism sustains effector T cell function through cell-surface glycosylation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:25Z",
  "url": "https://research.draconitic.com/paper/5wqcv8ty9xqts",
  "venue": "bioRxiv",
  "versions": []
}