{"id":357,"title":"A multi-center, single-arm, phase 2 trial of dasatinib in T follicular helper cell lymphomas","title_zh":"达沙替尼治疗T滤泡辅助细胞淋巴瘤的多中心单臂2期试验","url":"https://pubmed.ncbi.nlm.nih.gov/42967949","doi":"10.1038/s41467-026-78100-z","pmid":"42967949","journal":"Nat Commun","kind":"paper","lang":"en","published_at":"2026-10-05T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Suma S","Sakata-Yanagimoto M","Suehara Y","Ara T","Goto H","Usuki K","Izutsu K","Yamaguchi M","Fukuhara N","Sakaida E","Ohmachi K","Uehara A","Matsue K","Kimura S","Nagai H","Maruyama D","Nishimoto M","Takeuchi K","Nakamura N","Terauchi T","Fujisawa M","Abe Y","Makishima K","Hattori K","Sakamoto T","Kurita N","Nishikii H","Yoshino F","Yoshida K","Hashimoto Y","Kaneta T","Ogawa S","Keino N","Gosho M","Hosokawa H","Steidl C","Hashimoto K","Chiba S"],"primary_topic":"oocyte","topics":[{"slug":"oocyte","score":4.0,"hits":["follicular"]},{"slug":"omics-methods","score":1.0,"hits":["single-cell rna"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":38.0,"final_score":46.0,"score_dims":{"novelty":68,"rigor":62,"impact":15,"relevance":8,"translation":12},"recommend_reason":"该研究为肿瘤血液领域的阴性2期试验，虽含单细胞免疫微环境探索，但与生殖医学、辅助生殖及胚胎多组学无直接关系，不建议作为生殖领域每日必读内容。","keywords":["达沙替尼","T滤泡辅助细胞淋巴瘤","RHOA","TET2","单细胞RNA测序"],"selected":0,"story_id":null,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"nat-commun","journal_tier":"cns-sub","journal_if":14.7,"is_mock":false,"summary_zh":"该多中心单臂2期试验评估酪氨酸激酶抑制剂达沙替尼用于复发/难治性T滤泡辅助细胞淋巴瘤（TFHL）。共入组19例，18例接受治疗，17例可评估疗效；主要终点总体缓解率（ORR）为23.5%，低于预设30%阈值。携带TCR信号突变者ORR为36.4%，尤其RHOA p.G17V患者，突变阴性者无缓解。探索性单细胞RNA测序显示缓解者肿瘤微环境富集IFN-γ/TNF，外周细胞毒性T细胞克隆扩增；早期进展与非恶性免疫细胞（含CD8+ T细胞）高TET2突变负荷相关。结论：主要终点未达标，但提示TET2相关免疫功能障碍可能限制达沙替尼获益。","summary":"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.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}