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中国癌症防治杂志 ›› 2022, Vol. 14 ›› Issue (1): 87-93.doi: 10.3969/j.issn.1674-5671.2022.01.15

• 临床研究 • 上一篇    下一篇

肿瘤相关巨噬细胞与弥漫大B细胞淋巴瘤预后的关系

  

  1. 广西医科大学附属肿瘤医院 淋巴血液及儿童肿瘤科,病理科
  • 出版日期:2022-02-25 发布日期:2022-03-11
  • 通讯作者: 岑洪 E-mail:cen_hong@163.com
  • 基金资助:
    广西自然科学基金项目(2018GXNSFBA281026);广西壮族自治区卫生健康委员会自筹经费科研课题(Z20200883)

Relationship between tumor⁃associated macrophages and prognosis of diffuse large B⁃cell lymphoma

  • Online:2022-02-25 Published:2022-03-11

摘要: 目的 探讨肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)预后的关系。方法 收集2015年7月至2018年5月广西医科大学附属肿瘤医院收治的95例DLBCL患者的临床资料,采用免疫组化法检测DLBCL组织中CD68、CD163的表达水平,并分析TAMs浸润水平与DLBCL患者临床特征及预后的关系,并在公共数据库GSE31312、GSE10846基因表达数据集进行验证;利用ssGSEA方法探讨TAMs中M2型影响预后的潜在免疫生物学机制。结果 95例DLBCL患者中,CD68+TAMs低表达50例(52.6%),高表达45例(47.4%);CD163+TAMs低表达和高表达分别为34例(35.8%)和61例(64.2%)。CD68+TAMs浸润水平与血清乳酸脱氢酶水平、AnnArbor分期、骨髓受侵相关(均P<0.05),而CD163+TAMs浸润水平与患者临床病理参数均无关(均P>0.05)。Kaplan-Meier生存分析显示,DLBCL组织中CD68+TAMs、CD163+TAMs高浸润与患者较短生存时间相关(均P<0.05);多因素Cox回归分析显示DLBCL组织中CD163+TAMs高浸润是患者预后的独立危险因素(HR=2.695,95%CI:1.126~6.455,P=0.026)。ssGSEA富集分析有6条免疫相关信号通路(适应性免疫系统通路、MHCⅠ类抗原呈递信号通路、Ⅰ型干扰素信号通路、Treg分化信号通路、TCR信号通路、趋化因子信号通路)在M2型TAMs低浸润组显著富集(均P<0.05,FDR<0.25)。结论 DLBCL组织中CD163+TAMs高浸润水平是患者预后的独立危险因素,且可能通过调节免疫相关信号通路影响患者预后。

关键词: 弥漫大B细胞淋巴瘤, 肿瘤相关巨噬细胞, 免疫相关信号通路, 预后

Abstract:  Objective To investigate the relationship between tumor-associated macrophages (TAMs) and the prognosis of diffuse large B-cell lymphoma (DLBCL). Methods The clinical data of 95 DLBCL patients admitted to Guangxi Medical University Cancer Hospital from July 2015 to May 2018 were collected. The expression levels of CD68 and CD163 in 95 DLBCL tissues were detected by immunohistochemistry. The relationship between the TAMs infiltration level and the clinical characteristics and prognosis of DLBCL patients was analyzed, and verified in the public database GSE31312 and GSE10846 gene expression datasets. The ssGSEA method was used to investigate the potential immunobiological mechanism behind the influence of M2-type TAMs on the prognosis. Results Among 95 DLBCL patients, 50 cases (52.6%) had low expression of CD68+TAMs, and 45 cases (47.4%) had high expression; 34 cases (35.8%) and 61 cases (64.2%) had low and high expression of CD163+TAMs, respectively. The level of CD68+TAMs infiltration was correlated with lactate dehydrogenase level, AnnArbor stage and bone marrow invasion (all P<0.05), while the level of CD163+TAMs infiltration were not correlated with patients clinicopathological parameters (all P>0.05). Kaplan-Meier survival analysis showed that high infiltration of CD68+TAMs and CD163+TAMs in DLBCL tissues was associated with shorter survival time of patients (all P<0.05). Multivariable Cox regression analysis showed that high infiltration level of CD163+TAMs in DLBCL tissues was an independent risk factor for prognosis of patients (HR=2.695, 95%CI: 1.126-6.455, P=0.026). ssGSEA enrichment analysis showed 6 immune-related signaling pathways (Adaptive immune system pathway, MHC classⅠantigen presentation pathway, TypeⅠinterferon signaling pathway, Treg differentiation signaling pathway, TCR signaling pathway and Chemokine signaling pathway) were significantly enriched in the M2-type TAMs low infiltration group (all P<0.05, FDR<0.25). Conclusions The high infiltration level of CD163+TAMs in DLBCL tissues is an independent risk factor affecting the prognosis of patients, which may affect the prognosis of DLBCL by regulating immune-related signaling pathways.

Key words: Diffuse large B-cell lymphoma, Tumor-associated macrophages, Immune-related signaling pathway, Prognosis

中图分类号: 

  • R733.4