{
  "abstract": "Tissue microenvironments differ widely in nutrient composition; yet how local nutrient conditions shape epigenetic programs that direct immune cell fate is poorly understood. We identify histone lysine propionylation (Kpr) as a chromatin mechanism linking nutrient availability to T cell fate decisions. Proteomic analysis reveals that Kpr is broadly reduced in exhausted T cells. H3K18pr is enriched at stemness-associated loci in effector T cells and depleted upon exhaustion. Isoleucine and propionate supply propionyl-CoA in T cells, and restricted nutrient availability within the tumor microenvironment limits histone Kpr, promoting T cell exhaustion. Disrupting isoleucine catabolism in T cells further suppresses Kpr, without altering histone acetylation, and impairs T cell function and antitumor immunity in a manner rescued by propionate. Dietary supplementation of isoleucine and propionate increases Kpr in tumor infiltrating lymphocytes, limits exhaustion, and improves tumor control. These findings establish a microenvironment-chromatin axis crucial for antitumor immunity and amenable to nutritional intervention.",
  "abstract_shown": true,
  "affiliations": [
    "Temple University Lewis Katz School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "name": "A. Jaccard"
    },
    {
      "name": "K. Rome"
    },
    {
      "name": "Q. Yang"
    },
    {
      "name": "S. Zhang"
    },
    {
      "name": "N. Ford"
    },
    {
      "name": "A. Chatoff"
    },
    {
      "name": "T. N. Van Le"
    },
    {
      "name": "M. Noji"
    },
    {
      "name": "A. Andress Huacachino"
    },
    {
      "name": "S. Stransky Lauar"
    },
    {
      "name": "C. Pondevida"
    },
    {
      "name": "K. Trihemasava"
    },
    {
      "name": "L. V. Pinheiro"
    },
    {
      "name": "S. Bhadsalve"
    },
    {
      "name": "E. K. Ko"
    },
    {
      "name": "C. Salinas"
    },
    {
      "name": "M. M. Marcinkiewicz"
    },
    {
      "name": "B. C. Capell"
    },
    {
      "name": "G. Vahedi"
    },
    {
      "name": "S. Sidoli"
    },
    {
      "name": "R. S. OConnor"
    },
    {
      "name": "W. Bailis"
    },
    {
      "affs": [
        0
      ],
      "name": "N. W. Snyder"
    },
    {
      "name": "K. E. Wellen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4mw4xpnz8xz0z.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.01.756002",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756002v1.full",
  "id": "4mw4xpnz8xz0z",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756002v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7220684091",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756002v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4mw4xpnz8xz0z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:19Z",
      "native_id": "10.64898/2026.10.01.756002",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756002v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Nutrient-sensitive histone propionylation regulates T cell fate and function",
  "title_text": "Nutrient-sensitive histone propionylation regulates T cell fate and function",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:19Z",
  "url": "https://research.draconitic.com/paper/4mw4xpnz8xz0z",
  "venue": "bioRxiv",
  "versions": []
}