{
  "abstract": "Bladder cancer is increasingly treated with platinum chemotherapy, immune checkpoint blockade, and antibody-drug conjugates, but treatment resistance remains common. Methionine connects nutrient availability with S-adenosylmethionine (SAM) production, methylation, redox homeostasis, and lymphocyte function. In cisplatin-resistant tumor cells, MAT2A stabilization sustains a SAM-dependent program of stem-like renewal and drug resistance. Concurrently, increased SLC7A6-associated methionine uptake can create a tumor methionine sink that lowers methionine and SAM in CD8+ T cells, weakens H3K79me2-STAT5 signaling, and impairs effector function. Separately, methionine-sensitive YTHDF1 signaling suppresses RIG-I-dependent innate sensing and increases PD-L1 translation. A layered metabolic immune checkpoint is proposed to explain how these convergent but non-equivalent mechanisms link treatment-selected tumor fitness, nutrient competition, and reduced immune visibility. The framework exposes a context-dependent therapeutic paradox: methionine restriction may weaken tumor adaptation but compromise T-cell fitness, whereas SAM restoration may support antitumor immunity while also fueling malignant cells. Therefore, treatment-state biomarkers should guide compartment-selective targeting and intervention timing.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, The First Hospital of China Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chengyuan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhe Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianbin Bi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/85a6jxe819hyg.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1965813",
  "fulltext_url": null,
  "id": "85a6jxe819hyg",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1965813/full",
  "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": [
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7223180636",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1965813/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/85a6jxe819hyg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1965813",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1965813/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Therapy-induced methionine competition in bladder cancer: MAT2A-SAM axis remodeling as a metabolic immune checkpoint",
  "title_text": "Therapy-induced methionine competition in bladder cancer: MAT2A-SAM axis remodeling as a metabolic immune checkpoint",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/85a6jxe819hyg",
  "venue": "Frontiers in Immunology",
  "versions": []
}