Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hematol Oncol. 2021 Dec;39(5):616-624. doi: 10.1002/hon.2905. Epub 2021 Jul 31.
Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with complex tumor microenvironment (TME) alterations. However, immune cell signatures of TME and their prognostic value remain unclear in DLBCL. We aimed to identify high-risk DLBCL with specific immune cell signatures in TME. Clinical and gene expression data of DLBCL patients were obtained from previously reported retrospective datasets in Gene Expression Omnibus (GSE10846 and GSE53786 ) and a multi-center prospective clinical trial NHL001 (NCT01852435). Patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (n = 159) from GSE10846 were referred as training cohort for CHOP regimen, while patients treated with rituximab-CHOP (R-CHOP) regimen (n = 192) from GSE10846 as training cohort for R-CHOP regimen. Patients from NHL001 (n = 68) and GSE53786 (n = 57) were referred as validation cohorts for R-CHOP regimen. CIBERSORT was applied to estimate the relative proportions of 22 subtype of immune cells. We established a prognostic model for model for R-CHOP regimen included Age, performance status, lactate dehydrogenase, T cells follicular helper and macrophages M0, defining a low-risk group with 2-years OS of 92.9% and a high-risk group with 2-years OS of 52.5% (HR 6.57 [3.27-13.18], p < 0.0001). Immune cell signatures could be used as prognostic markers and provided further insights for individualized immunotherapeutic strategies in DLBCL.
弥漫性大 B 细胞淋巴瘤 (DLBCL) 是一种遗传异质性疾病，其肿瘤微环境 (TME) 存在复杂的改变。然而，TME 中的免疫细胞特征及其预后价值在 DLBCL 中仍不清楚。我们旨在确定 TME 中具有特定免疫细胞特征的高危 DLBCL。从先前报道的基因表达 Omnibus (GSE10846 和 GSE53786) 和多中心前瞻性临床试验 NHL001 (NCT01852435) 中获得 DLBCL 患者的临床和基因表达数据。来自 GSE10846 的接受环磷酰胺、多柔比星、长春新碱和泼尼松 (CHOP) 方案治疗的患者 (n = 159) 被称为 CHOP 方案的训练队列，而来自 GSE10846 的接受利妥昔单抗-CHOP (R-CHOP) 方案治疗的患者 (n = 192) 被称为 R-CHOP 方案的训练队列。来自 NHL001 (n = 68) 和 GSE53786 (n = 57) 的患者被称为 R-CHOP 方案的验证队列。应用 CIBERSORT 估计 22 种免疫细胞亚型的相对比例。我们建立了一个用于 R-CHOP 方案的预后模型，该模型包括年龄、体能状态、乳酸脱氢酶、滤泡辅助性 T 细胞和 M0 巨噬细胞，定义了 2 年 OS 为 92.9%的低危组和 2 年 OS 为 52.5%的高危组 (HR 6.57 [3.27-13.18]，p < 0.0001)。免疫细胞特征可用作预后标志物，并为 DLBCL 的个体化免疫治疗策略提供了进一步的见解。
