文章：

慢性淋巴细胞白血病与Richter综合征具有不同的免疫特征

Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome

原文发布日期：2021-05-10

DOI: 10.1038/s41408-021-00477-5

类型: Article

开放获取: 是

英文摘要：

Richter syndrome (RS) refers to transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. RS is known to be associated with a number of genetic alterations such as TP53 and NOTCH1 mutations. However, it is unclear what immune microenvironment changes are associated with RS. In this study, we analyzed expression of immune checkpoint molecules and infiltration of immune cells in nodal samples, and peripheral blood T-cell diversity in 33 CLL and 37 RS patients. Compared to CLL, RS nodal tissue had higher PD-L1 expression in histiocytes and dendritic cells (median 16.6% vs. 2.8%, P < 0.01) and PD1 expression in neoplastic B cells (median 26.0% vs. 6.2%, P < 0.01), and higher infiltration of FOXP3-positive T cells (median 1.7% vs. 0.4%, P < 0.01) and CD163-positive macrophages (median 23.4% vs. 9.1%, P < 0.01). In addition, peripheral blood T-cell receptor clonality was significantly lower in RS vs. CLL patients (median [25th–75th], 0.107 [0.070–0.209] vs. 0.233 [0.111–0.406], P = 0.046), suggesting that T cells in RS patients were significantly more diverse than in CLL patients. Collectively these data suggest that CLL and RS have distinct immune signatures. Better understanding of the immune microenvironment is essential to improve immunotherapy efficacy in CLL and RS.
 

摘要翻译： 

里氏综合征（RS）指慢性淋巴细胞白血病（CLL）转化为侵袭性淋巴瘤，最常见为弥漫性大B细胞淋巴瘤。已知RS与多种基因改变相关，如TP53和NOTCH1突变。然而，目前尚不清楚哪些免疫微环境变化与RS相关。本研究分析了33例CLL和37例RS患者的淋巴结样本中免疫检查点分子表达、免疫细胞浸润情况以及外周血T细胞多样性。与CLL相比，RS淋巴结组织中组织细胞和树突状细胞的PD-L1表达更高（中位数16.6% vs. 2.8%，P<0.01），肿瘤性B细胞的PD1表达更高（中位数26.0% vs. 6.2%，P<0.01），FOXP3阳性T细胞（中位数1.7% vs. 0.4%，P<0.01）和CD163阳性巨噬细胞浸润更显著（中位数23.4% vs. 9.1%，P<0.01）。此外，RS患者外周血T细胞受体克隆性显著低于CLL患者（中位数[第25-75百分位数]，0.107 [0.070-0.209] vs. 0.233 [0.111-0.406]，P=0.046），表明RS患者的T细胞多样性显著高于CLL患者。这些数据共同表明CLL与RS具有不同的免疫特征。深入理解免疫微环境对于提高CLL和RS的免疫治疗效果至关重要。

原文链接：

Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome