决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Highly Skewed Immunohistochemical αβ:γδ Ratios for T-Cell Receptors Can Be Detected in Reactive Duodenal Biopsies: A Potential Pitfall in the Diagnosis of T-Cell Lymphoma.
背景:T细胞受体(TCR)分为α链和β链两组。
背景:T 细胞受体(TCR)分为 αβ 链组和 γδ 链组。已有研究表明,T 细胞淋巴瘤(TCL)可表达 αβ 或 γδ TCR。针对 TCR-BetaF1(TCR-BF1)(βF1)和 TCR-delta(δ)的免疫组织化学染色已在临床上用于对各种器官的 TCL 进行分类和诊断。除乳糜泻外,十二指肠内 T 细胞 TCR-BF1 和 TCR-delta 的表达与分布在很大程度上仍不清楚。 目的:检测 TCR-BF1 和 TCR-delta 在各种十二指肠病理过程中的表达。 方法:我们收集了 50 例十二指肠活检标本,其病因为各种炎症性和感染性因素,例如乳糜泻、炎症性肠病、蛋白丢失性肠病、CAR-T 细胞相关肠炎以及免疫检查点抑制。另纳入 5 例无病理发现的病例和 3 例 TCL 病例以供比较。我们在活检组织上进行了 CD3、TCR-BF1 和 TCR-delta 的免疫组织化学染色。通过低倍视野估测和人工高倍视野计数,评估 T 细胞中 TCR-BF1:TCR-delta 的比值以及 T 细胞在十二指肠黏膜中的相对分布。 结果:在所有非 TCL 病例中,TCR-BF1 T 细胞均比 TCR-delta T 细胞更为多见。乳糜泻的 TCR-BF1:TCR-delta 偏斜程度低于其他疾病(均值 1.97 对 26.21-320)。 结论:在正常十二指肠及多种非肿瘤性病变中,十二指肠 T 细胞表达 TCR-BF1 均比 TCR-delta 更为普遍。除乳糜泻外,在此类十二指肠活检标本中,TCR-BF1:TCR-delta T 细胞比值可高度偏向 TCR-BF1。因此,通过免疫组织化学评估TCR-BF1:TCR-delta T细胞比率可能错误地推断T细胞单克隆性,在评估T细胞淋巴瘤时应谨慎解读。
CONTEXT.—: T-cell receptors (TCRs) are classified as - and -chain groups. T-cell lymphoma (TCL) has been shown to express either or TCRs. Immunohistochemical stains for TCR-BetaF1 (TCR-BF1) ( ) and TCR-delta ( ) have been used clinically for classifying and diagnosing TCL in various organs. Outside of celiac disease, T-cell expression and distribution of TCR-BF1 and TCR-delta in the duodenum are largely unknown. OBJECTIVE.—: To examine TCR-BF1 and TCR-delta expression in various duodenal pathologic processes. DESIGN.—: We collected 50 duodenal biopsy specimens with various inflammatory and infectious etiologies, such as celiac disease, inflammatory bowel disease, protein-losing enteropathy, chimeric antigen receptor T-cell (CAR-T)-related enteritis, and immune checkpoint inhibition. Five cases with no pathologic findings and 3 TCL cases were included for comparison. We performed immunohistochemistry for CD3, TCR-BF1, and TCR-delta on biopsy tissue. Low-power field estimates and manual high-power field counts were performed to assess TCR-BF1:TCR-delta ratios in T cells and the relative distribution of T cells in duodenal mucosa. RESULTS.—: In all non-TCL cases, TCR-BF1 T cells were more prevalent than TCR-delta T cells. Celiac disease showed less TCR-BF1:TCR-delta skewing than other conditions (mean, 1.97 versus 26.21-320). CONCLUSIONS.—: Expression of TCR-BF1 is more prevalent than TCR-delta in duodenal T cells in normal duodenum and across multiple nonneoplastic processes. Outside of celiac disease, the TCR-BF1:TCR-delta T-cell ratios can be highly skewed toward TCR-BF1 in such duodenal biopsy samples. As such, the assessment of TCR-BF1:TCR-delta T-cell ratios via immunohistochemistry can mistakenly infer T-cell monoclonality and thus should be interpreted with caution in the assessment of T-cell lymphoma.
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