Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.
Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.
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DOI：
10.1056/nejmoa0905680
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发表时间：
2010-03-11
期刊：
影响因子：
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通讯作者：
Gascoyne RD
中科院分区：
文献类型：
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作者：
Steidl C;Lee T;Shah SP;Farinha P;Han G;Nayar T;Delaney A;Jones SJ;Iqbal J;Weisenburger DD;Bast MA;Rosenwald A;Muller-Hermelink HK;Rimsza LM;Campo E;Delabie J;Braziel RM;Cook JR;Tubbs RR;Jaffe ES;Lenz G;Connors JM;Staudt LM;Chan WC;Gascoyne RD
尽管霍奇金淋巴瘤的治疗方法取得了进展，但仍有约20%的患者死于进展性疾病。目前的预后模型对治疗结果的预测并不完全准确，临床上相关的生物标志物还没有建立起来以改善国际预后评分。利用基因表达谱，我们分析了130例典型霍奇金淋巴瘤患者在诊断淋巴结活检过程中获得的冰冻样本，以确定哪些细胞特征与治疗结果相关。我们使用免疫组织化学分析，在166名患者的独立队列中证实了我们的发现。基因表达谱确定了肿瘤相关巨噬细胞的基因特征，该特征与初次治疗失败显著相关(P=0.02)。在一组独立的患者中，我们发现CD68+巨噬细胞数量的增加与无进展生存期缩短(P=0.03)和自体造血干细胞移植后复发的可能性增加(P=0.008)相关，从而导致疾病特异性生存期缩短(P=0.003)。在多变量分析中，这种不利的预后因素优于疾病特定生存的国际预后评分(P=0.003.0 1比P=0.0 3)。在有限分期疾病患者中，CD68+细胞的数量没有增加，这定义了在使用当前治疗策略的情况下，疾病特异性长期存活率为100%的患者亚组。肿瘤相关巨噬细胞数量的增加与典型霍奇金淋巴瘤患者的生存期缩短密切相关，并为风险分层提供了一个新的生物标志物。
Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score. Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis. Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P = 0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P = 0.03) and with an increased likelihood of relapse after autologous hematopoietic stem-cell transplantation (P = 0.008), resulting in shortened disease-specific survival (P = 0.003). In multivariate analysis, this adverse prognostic factor outperformed the International Prognostic Score for disease-specific survival (P = 0.003 vs. P = 0.03). The absence of an elevated number of CD68+ cells in patients with limited-stage disease defined a subgroup of patients with a long-term disease-specific survival of 100% with the use of current treatment strategies. An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma and provides a new biomarker for risk stratification.