{
  "abstract": "T follicular helper cell lymphomas (TFHL) harbor activating T cell receptor (TCR) signaling mutations and epigenetic alterations, such as TET2 mutations. Here, we conduct a multi-center, single-arm, phase 2 trial of the tyrosine kinase inhibitor dasatinib in patients with relapsed/refractory TFHLs (jRCT2031190079). The primary outcome is the overall response rate (ORR) according to CT-based Lugano criteria 2014. Key secondary endpoints include ORR in RHOA-mutated patients and progression-free/overall survival. The main inclusion criteria consist of TFHL diagnosis and relapse following at least 1 prior chemotherapy regimen. Key exclusion criteria encompass central nervous system involvement, history of other malignancies, and receipt of chemotherapy or radiotherapy within 4 weeks. Nineteen patients are enrolled, with 18 receiving dasatinib and 17 evaluable for efficacy. Median age is 73 years, 50% are female, and angioimmunoblastic T cell lymphoma is the predominant subtype (n = 13). Dasatinib yields a 23.5% ORR, below the prespecified 30% endpoint. Treatment-related adverse events occur in 61.1% of patients (n = 11). Patients harboring TCR signaling mutations, especially those with RHOA p.G17V, achieve a 36.4% ORR, whereas no responses are observed in mutation-negative cases. Exploratory single-cell RNA sequencing reveals interferon-γ/tumor necrosis factor-enriched tumor microenvironments and peripheral expansion of cytotoxic T cell clones in responders. Conversely, early progression correlates with a high TET2 mutation burden in non-malignant immune cells, including CD8⁺ T cell subsets. While the primary outcome is below the prespecified endpoint, our exploratory findings implicate immune dysfunction involving TET2 mutations in limiting the therapeutic benefit of dasatinib.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 38,
  "authors": [
    {
      "name": "Sakurako Suma",
      "orcid": "0000-0003-2491-3798"
    },
    {
      "name": "Mamiko Sakata-Yanagimoto",
      "orcid": "0000-0001-7310-8045"
    },
    {
      "name": "Yasuhito Suehara"
    },
    {
      "name": "Takahide Ara",
      "orcid": "0000-0001-9609-3202"
    },
    {
      "name": "Hideki Goto"
    },
    {
      "name": "Kensuke Usuki",
      "orcid": "0000-0002-1216-4470"
    },
    {
      "name": "Koji Izutsu",
      "orcid": "0000-0001-9129-8057"
    },
    {
      "name": "Motoko Yamaguchi"
    },
    {
      "name": "Noriko Fukuhara",
      "orcid": "0000-0003-2682-2179"
    },
    {
      "name": "Emiko Sakaida",
      "orcid": "0000-0002-7254-1928"
    },
    {
      "name": "Ken Ohmachi"
    },
    {
      "name": "Atsushi Uehara"
    },
    {
      "name": "Kosei Matsue"
    },
    {
      "name": "Satoshi Kimura"
    },
    {
      "name": "Hirokazu Nagai"
    },
    {
      "name": "Dai Maruyama"
    },
    {
      "name": "Mitsutaka Nishimoto"
    },
    {
      "name": "Kengo Takeuchi",
      "orcid": "0000-0002-1599-5800"
    },
    {
      "name": "Naoya Nakamura"
    },
    {
      "name": "Takashi Terauchi"
    },
    {
      "name": "Manabu Fujisawa",
      "orcid": "0009-0007-1122-6549"
    },
    {
      "name": "Yoshiaki Abe",
      "orcid": "0000-0002-1021-7911"
    },
    {
      "name": "Kenichi Makishima"
    },
    {
      "name": "Keiichiro Hattori"
    },
    {
      "name": "Tatsuhiro Sakamoto",
      "orcid": "0000-0001-6852-0721"
    },
    {
      "name": "Naoki Kurita"
    },
    {
      "name": "Hidekazu Nishikii",
      "orcid": "0000-0002-6277-4082"
    },
    {
      "name": "Futoshi Yoshino"
    },
    {
      "name": "Kenichi Yoshida",
      "orcid": "0000-0003-4612-2778"
    },
    {
      "name": "Yuko Hashimoto"
    },
    {
      "name": "Tomohiro Kaneta"
    },
    {
      "name": "Seishi Ogawa"
    },
    {
      "name": "Naoto Keino",
      "orcid": "0009-0004-2482-8459"
    },
    {
      "name": "Masahiko Gosho"
    },
    {
      "name": "Hiroyuki Hosokawa"
    },
    {
      "name": "Christian Steidl",
      "orcid": "0000-0001-9842-9750"
    },
    {
      "name": "Koichi Hashimoto"
    },
    {
      "name": "Shigeru Chiba"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2qy3qcf8a5e9n.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78100-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13724723",
  "id": "2qy3qcf8a5e9n",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78100-z",
  "language": "eng",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2734|Lymphoma Diagnosis and Treatment"
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  "openalex": "W7220392226",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78100-z_reference.pdf",
  "pmcid": "PMC13724723",
  "pmid": "42967949",
  "published": "2026-10-05",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/2qy3qcf8a5e9n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Lymphoma Diagnosis and Treatment",
      "subfield": "general"
    }
  ],
  "title": "A multi-center, single-arm, phase 2 trial of dasatinib in T follicular helper cell lymphomas",
  "title_text": "A multi-center, single-arm, phase 2 trial of dasatinib in T follicular helper cell lymphomas",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:08Z",
  "url": "https://research.draconitic.com/paper/2qy3qcf8a5e9n",
  "venue": "Nature Communications",
  "versions": []
}