Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer
Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer
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DOI：
10.1200/jco.2008.18.7229
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发表时间：
2009-01-10
影响因子：
45.3
通讯作者：
Iacopetta, Barry
中科院分区：
文献类型：
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作者：
Salama, Paul;Phillips, Michael;Iacopetta, Barry
目的探讨FOXP3（+）淋巴细胞（Treg）密度与常规组织病理学特征及CD8（+）和CD45RO（+）淋巴细胞密度的比较对结直肠癌预后的意义。方法采用组织微阵列技术和免疫组化技术对967例II期和III期结直肠癌患者的肿瘤组织和正常结肠黏膜中CD8（+）、CD45RO（+）和FOXP3（+）淋巴细胞的密度进行检测。评估其与组织病理特征和患者生存的关系。结果肿瘤组织中foxp3 (+) Treg细胞密度高于正常结肠黏膜，而CD8（+）和CD45RO（+）细胞密度低于正常结肠黏膜。除肿瘤分期外，FOXP3(+) Tregs与任何组织病理学特征均无相关性。多因素分析显示，分期、血管浸润、正常组织和肿瘤组织FOXP3(+) Treg密度是独立的预后指标，而CD8（+）和CD45RO（+）不是独立的预后指标。正常黏膜FOXP3(+) Treg密度高与预后差相关（风险比[HR] = 1.51; 95% CI, 1.07 ~ 2.13; P = 0.019）。相比之下，肿瘤组织中FOXP3(+) Tregs的高密度与生存率的提高相关（HR = 0.54; 95% CI, 0.38 ~ 0.77; P = 0.001）。结论与CD8（+）和CD45RO（+）淋巴细胞相比，正常组织和肿瘤组织中foxp3 (+) Treg密度对结直肠癌的预后有更强的意义。与其他几种实体癌相比，结直肠癌中肿瘤浸润性FOXP3(+) Tregs的高密度与生存率的提高有关。FOXP3(+) Treg密度的检测可能有助于改善早期结直肠癌的预后。
PurposeTo determine the prognostic significance of FOXP3(+) lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8(+) and CD45RO(+) lymphocyte densities.Patients and MethodsTissue microarrays and immunohistochemistry were used to assess the densities of CD8(+), CD45RO(+), and FOXP3(+) lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival.ResultsFOXP3(+) Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8(+) and CD45RO(+) cell densities were lower. FOXP3(+) Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3(+) Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8(+) and CD45RO(+). High FOXP3(+) Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3(+) Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001).ConclusionFOXP3(+) Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8(+) and CD45RO(+) lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3(+) Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3(+) Treg density may help to improve the prognostication of early-stage colorectal cancer.