Blood:单细胞测序揭示淋巴瘤再与T细胞免疫检查点的共表达基因

2019-01-21 MedSci MedSci原创

中心点:恶性滤泡淋巴瘤B细胞分离成多个共存的亚克隆,其特点是通路活性不同。在CD4+Tregs细胞中,已知的免疫检查点基因与转录因子和免疫调节基因共表达,包括CEBPA和B2M。摘要:滤泡淋巴瘤(FL)是低级别的B细胞恶性肿瘤,可转化成高侵袭性的致死性疾病,每年发生率约2%。从外科活检中完美分离恶性B细胞群是一个重大挑战,遮盖了重要的FL生物学特性,如免疫检查点共表达模式。为探究滤泡B细胞淋巴瘤的

中心点:

恶性滤泡淋巴瘤B细胞分离成多个共存的亚克隆,其特点是通路活性不同。

在CD4+Tregs细胞中,已知的免疫检查点基因与转录因子和免疫调节基因共表达,包括CEBPA和B2M。

摘要:

滤泡淋巴瘤(FL)是低级别的B细胞恶性肿瘤,可转化成高侵袭性的致死性疾病,每年发生率约2%。从外科活检中完美分离恶性B细胞群是一个重大挑战,遮盖了重要的FL生物学特性,如免疫检查点共表达模式。

为探究滤泡B细胞淋巴瘤的潜在转录网络,Noemi Andor等人分析了6个原发性FL肿瘤的34188个细胞的转录本。研究人员通过基因表达鉴别每一个肿瘤的正常的免疫亚群和恶性B细胞。同时采用多色流式细胞术分析同种肿瘤来确认对细胞谱系分类,并验证对表达蛋白的预测。

对比同一患者匹配的恶性B细胞和正常B细胞的基因表达明确肿瘤特异性。恶性B细胞的免疫球蛋白轻链表达受限,BCL2基因上调,FCER2、CD52、 II类MHC基因下调。通过对每个患者的数千个肿瘤细胞进行分析,研究人员明确了共存于FL恶性B细胞亚克隆中的嵌合体。研究人员鉴定出与免疫检查点分子共表达的基因,如在Treg细胞中的CEBPA和B2M,有助于更好的理解免疫调控的基因网络。

总而言之,平行检测数千个肿瘤细胞和肿瘤浸润淋巴细胞的单细胞表达,可以获得肿瘤微环境的整体观,开发新的治疗方法。

原始出处:

Noemi Andor, et al.Single-cell RNA-Seq of lymphoma cancers reveals malignant B cell types and co-expression of T cell immune checkpoints.Blood 2018 :blood-2018-08-862292; doi: https://doi.org/10.1182/blood-2018-08-862292 

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    2019-01-28 1e145228m78(暂无匿称)

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