肿瘤细胞治疗研究
英文原题：Case Report: An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing.
Case Report: An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing.
我们发现了首例共表达 、和 链的 TCL 病例，并剖析了其分子发病机制，为这一新型 TCL 亚型的精准医学选择提供了有价值的信息。
背景：T细胞淋巴瘤（TCL）是一组异质性疾病，包括40余种亚型。本研究发现一种新型TCL亚型，其特征是单个恶性T细胞中共表达T细胞受体（TCR）αβ链和γ链。病例介绍：一名45岁男性出现腹胀和肝大2个月后确诊T细胞淋巴瘤。结合组织学复核、PET-CT检查和免疫表型，无法将该病例归入任何现有TCL亚型。为深入了解这一未分类TCL病例，研究人员对患者外周血单个核细胞（PBMC）和骨髓样本进行单细胞RNA测序及配对TCR测序。令人意外的是，恶性T细胞呈现极罕见的TCR组合，同时表达两条不同TCR链组合。研究人员进一步探讨这一罕见TCL亚型的分子发病机制和肿瘤细胞异质性，并从转录组数据中发现一组潜在治疗靶点，如CCL5、KLRG1和CD38。结论：本研究首次发现共表达αβ链和γ链的TCL病例，并解析其分子发病机制，为这一新型TCL亚型的精准医疗提供了有价值的信息。
BACKGROUND: T cell lymphomas (TCL) are a group of heterogeneous diseases with over 40 subtypes. In this study, we identified a novel TCL subtype which was featured by a unique T cell receptor (TCR) presentation, , and chains were co-existing in a single malignant T cell. CASE PRESENTATION: A 45-year-old male patient was diagnosed T cell lymphoma after 2-month of abdominal distension and liver enlargement. Combining histology review, PET-CT scanning and immunophenotyes, the patient was not classified to any existing TCL subtypes. To better understand this unclassified TCL case, we performed single cell RNA sequencing paired with TCR sequencing on the patient's PBMC and bone marrow samples. To our surprise, we identified that the malignant T cells had a very rare TCR combination, by expressing two chains, one chain and one chain simultaneously. We further studied the molecular pathogenesis and tumor cell heterogeneity of this rare TCL subtype. A set of potential therapeutic targets were identified from the transcriptome data, such as CCL5, KLRG1 and CD38. CONCLUSIONS: We identified the first TCL case co-expressing , and chains and dissected its molecular pathogenesis, providing valuable information for precision medicine options for this novel TCL subtype.
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