PDL1/PDL2 基因高表达与原发性纵隔大 B 细胞淋巴瘤的较差预后相关。
High PDL1/PDL2 gene expression correlates with worse outcome in primary mediastinal large B-cell lymphoma.
发表日期：2023 Oct 20
作者：
Vincent Camus, Pierre-Julien Viailly, Fanny Drieux, Elena-Liana Veresezan, Pierre Sesques, Corinne Haioun, Eric Durot, Martine Patey, Cédric Rossi, Laurent Martin, Vinciane Rainville, Elodie Bohers, Philippe Ruminy, Dominique Penther, Sophie Kaltenbach, Julie Bruneau, Jérôme Paillassa, Olivier Tournilhac, Alexandre Willaume, Chloe Antier, Julien Lazarovici, Emilie Leveque, Pierre Decazes, Stéphanie Becker, David Tonnelet, Alina Berriolo-Riedinger, Philippe Gaulard, Herve Tilly, Thierry Jo Molina, Alexandra Traverse-Glehen, Fabrice Jardin
来源：
Blood Advances
摘要：
原发性纵隔 B 细胞淋巴瘤 (PMBL) 是一种罕见的侵袭性大 B 细胞淋巴瘤，预后异常良好，但 10-15% 的化疗难治性病例预后不良。为了识别化疗难治高风险患者，我们对接受一线免疫化疗治疗的 PMBL 患者的回顾性多中心队列进行了分子特征分析。具有基因表达谱 (GEP) 数据的患者 (n=120) 的特征如下：中位年龄 34 [18-67] 岁，女性 58.3%，LDH 升高 82.5%，ECOG 0- 1 85.7%，安娜堡 I-II 期 55%，IPI 1-2 64.4%，中位代谢肿瘤体积 290.4 [15.7-1147.5] cm3。在测试与生存数据相关性的所有 137 个标记物中，只有 PDL1 和 PDL2 表达显示出预后影响。总体而言，37 名 (30.8%) 患者中 PDL1 和 PDL2 基因均高表达（PDL1high/PDL2high；截止值：每个基因的中位表达：PDL1 = 0.402，PDL2 = 9.147）。 PDL1high/PDL2high 患者的基线临床特征与其他患者相似。在单变量分析中，PDL1high/PDL2high 状态与不良 PFS（HR=4.292，95% CI [1.447-12.817]）和 OS（HR=8.24 [1.71-39.7]）相关。在多变量分析中，PDL1high/PDL2high状态是不良结果的独立预后因素（PFS：HR= 5.22 [1.352-20.168]，OS：HR= 10.368 [1.204-89.267]）。我们在一个由 40 名患者组成的独立队列中验证了这些结果，并证实了 PDL1high/PDL2high 状态与较差 PFS 之间的显着相关性 (HR=6.11 [1.61-23.2])。 PDL1/PDL2 基因高表达定义了具有强大免疫特权但标准化疗效果不佳的人群，这些人群可能受益于一线抗 PD1 免疫治疗。版权所有 © 2023 美国血液学会。
Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive large B-cell lymphoma with an unusually good prognosis, except for 10-15% of chemorefractory cases with poor outcomes. To identify patients at high risk of chemorefractoriness, we performed molecular characterization of a retrospective multicenter cohort of PMBL patients treated with first-line immunochemotherapy. The traits of the patients with gene-expression profiling (GEP) data (n=120) were as follows: median [range] age of 34 [18-67] years, female sex 58.3%, elevated LDH 82.5%, ECOG 0-1 85.7%, Ann Arbor stage I-II 55%, IPI 1-2 64.4%, and median metabolic tumor volume 290.4 [15.7-1147.5] cm3. Among all 137 markers tested for correlation with survival data, only PDL1 and PDL2 expression showed a prognostic impact. Overall, both PDL1 and PDL2 genes were highly expressed in 37 (30.8%) patients (PDL1high/PDL2high; cutoff: median expression of each gene: PDL1 = 0.402, PDL2 = 9.147). The baseline clinical characteristics of PDL1high/PDL2high patients were similar to those of other patients. In univariate analysis, PDL1high/PDL2high status was associated with poor PFS (HR=4.292, 95% CI [1.447-12.817]) and OS (HR=8.24 [1.71-39.7]). In multivariate analysis, PDL1high/PDL2high status was an independent prognostic factor of adverse outcomes (PFS: HR= 5.22 [1.352-20.168], OS: HR= 10.368 [1.204-89.267]). We validated these results in an independent cohort of 40 patients and confirmed the significant association between PDL1high/PDL2high status and inferior PFS (HR=6.11 [1.61-23.2]). High PDL1/PDL2 gene expression defines a population with strong immune privilege and poor outcomes from standard chemotherapy who might benefit from first-line anti-PD1 immunotherapy.Copyright © 2023 American Society of Hematology.