Immune Profiles of Tumor Microenvironment and Clinical Prognosis among Women with Triple-Negative Breast Cancer

Immune Profiles of Tumor Microenvironment and Clinical Prognosis among Women with Triple-Negative Breast Cancer
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DOI:
10.1158/1055-9965.epi-19-0469
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发表时间:
2019-12-01
影响因子:
3.8
通讯作者:
Zheng, Hong
Zheng, Hong
中科院分区:
医学3区
文献类型:
--
作者:
Deng, Ling;Lu, Donghao;Zheng, Hong

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背景资料:微环境的免疫景观对癌症进展的影响对于三阴性乳腺癌(TNBC)还没有得到很好的理解。因此,我们的目的是检查免疫细胞富集评分作为肿瘤微环境免疫特征的代表与TNBC预后的相关性。方法:我们纳入了2008年至2016年在华西医院诊断的76例TNBC患者和158例来自癌症基因组图谱的TNBC患者。在转录组数据的基础上,我们使用基于基因签名的方法xCell计算了34种免疫细胞的总体免疫评分和类型特异性富集评分。采用考克斯比例风险模型计算无复发生存期(RFS)和总生存期(OS)的HR。结果:在中位2.8(0.1-9.8)年的随访时间内,42例患者复发,34例患者死亡。肿瘤中的总体免疫评分和大多数免疫细胞富集评分相对高于正常组织。较高的浆细胞富集评分与有利的RFS [HR 0.45; 95%置信区间(CI),0.27- 0.73]和OS(HR 0.32; 95% CI,0.17-0.61)相关。CD 4(+)中央记忆T细胞(Tcm)评分与RFS呈负相关(HR 1.52; 95% CI,1.17-1.97)。此外,浸润性肿瘤中非导管/小叶癌的CD 4 + Tcm富集评分较高(OR 1.59; 95%CI,1.06-2.37)。结论:我们的研究结果表明,肿瘤微环境中的浆细胞和CD 4(+)Tcm可能在TNBC的后续进展中发挥作用。这项研究提供了免疫细胞在TNBC进展中的作用的证据,可能具有临床实用性。
Background: The impact of the immune landscape of the microenvironment on cancer progression is not well understood for triple-negative breast cancer (TNBC). We, therefore, aimed to examine the association of immune cell enrichment scores as a proxy for immune profiles of tumor microenvironment with TNBC prognosis.Methods: We included 76 patients with TNBC diagnosed between 2008 to 2016 in West China Hospital and 158 patients with TNBC from The Cancer Genome Atlas. On the basis of transcriptome data, we calculated the overall Immune-Score and type-specific enrichment scores for 34 types of immune cells, using xCell, a gene signature-based method. HRs of recurrence-free survival (RFS) and overall survival (OS) were calculated by Cox proportional hazards models.Results: During the median follow-up time of 2.8 (0.1-9.8) years, 42 patients had a recurrence, and 34 patients died. The overall ImmuneScore and most immune cell enrichment scores were relatively higher in tumors than normal tissues. A higher enrichment score of plasma cells was associated with favorable RFS [HR 0.45; 95% confidence interval (CI), 0.27- 0.73] and OS (HR 0.32; 95% CI, 0.17-0.61). The score of CD4(+) central memory T cell (Tcm) was negatively associated with RFS (HR 1.52; 95% CI, 1.17-1.97). Besides, CD4+ Tcm enrichment score was higher in invasive tumors that were not ductal/lobular carcinoma (OR 1.59; 95% CI, 1.06-2.37).Conclusions: Our findings suggest that plasma cells and CD4(+) Tcm in the tumormicroenvironmentmay play a role in the subsequent progression of TNBC.Impact: This study provides evidence of the role of immune cells in TNBC progression that may have clinical utility.