Lamaison Claire, Ferrant Juliette, Gravelle Pauline, Traverse-Glehen Alexandra, Ghesquières Hervé, Tosolini Marie, Rossi Cédric, Ysebaert Loic, Brousset Pierre, Laurent Camille, Syrykh Charlotte
Centre Hospitalier Universitaire de Rennes, Pôle Biologie, 35033 Rennes, France.
Institut National de la Santé et de la Recherche Médicale, INSERM, Unité Mixte de Recherche U1236, Université Rennes 1, Établissement Français du Sang Bretagne, 35000 Rennes, France.
Cancers (Basel). 2022 Oct 6;14(19):4893. doi: 10.3390/cancers14194893.
Despite the success of standard front-line chemotherapy, 20% of classical Hodgkin lymphoma (cHL) patients still relapse or have refractory disease (r/r), and a subset of them die due to disease progression. There is a critical lack of predictive factors for early identification of those r/r patients who may benefit from new therapeutic strategies. This study aimed to evaluate the dynamic expression of 586 immune-related genes in a cohort of 42 cHL patients including 30 r/r cHL after first-line chemotherapy. Gene expression profiling (GEP) using NanoString technology identified a 19-gene immune signature at diagnosis predictive of cHL relapse, but dependent on histological subtypes. Genes related to tumor survival were found upregulated while genes related to B-lineage were downregulated at diagnosis in r/r nodular sclerosis cHL. In contrast to the mixed-cellularity subtype, comparative GEP analyses between paired diagnosis/relapse biopsies of nodular sclerosis cHL showed 118 differentially expressed genes, supporting an immune contexture switch at relapse with upregulation of immunosuppressive cytokines, such as and , and downregulation of the T-cell co-stimulatory receptor . These results indicate that the predictive value of immune signature in cHL is strongly influenced by histological subtype which should be considered when assessing new immunotherapy target strategies.
尽管一线标准化疗取得了成功，但仍有20%的经典型霍奇金淋巴瘤（cHL）患者会复发或患有难治性疾病（r/r），其中一部分患者会因疾病进展而死亡。目前严重缺乏预测因素，无法早期识别那些可能从新治疗策略中获益的r/r患者。本研究旨在评估42例cHL患者队列中586个免疫相关基因的动态表达，其中包括30例一线化疗后的r/r cHL患者。使用NanoString技术进行基因表达谱分析（GEP），在诊断时确定了一个由19个基因组成的免疫特征，可预测cHL复发，但依赖于组织学亚型。在r/r结节硬化型cHL诊断时，发现与肿瘤存活相关的基因上调，而与B细胞谱系相关的基因下调。与混合细胞亚型不同，结节硬化型cHL配对诊断/复发活检之间的比较GEP分析显示有118个差异表达基因，支持复发时免疫微环境的转变，免疫抑制细胞因子如 和 上调，T细胞共刺激受体下调。这些结果表明，cHL中免疫特征的预测价值受组织学亚型的强烈影响，在评估新的免疫治疗靶向策略时应予以考虑。
