Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma.
Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma.
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DOI：
10.1053/j.gastro.2009.06.053
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发表时间：
2009-10
期刊：
影响因子：
29.4
通讯作者：
Sargent DJ
中科院分区：
文献类型：
--
作者：
Sinicrope FA;Rego RL;Ansell SM;Knutson KL;Foster NR;Sargent DJ
Regulatory T cells (Tregs) express the forkhead box transcription factor (FoxP3) and suppress the anti-tumor immune response. We investigated whether the intratumoral densities of FoxP3+ and effector CD3+ lymphocytes are associated with prognosis of patients with colon cancer. FoxP3 and CD3 expression and location were determined in stage II and III colon carcinomas (n=160) and normal mucosa (n=25) by immunohistochemistry; CD4 and FoxP3 were localized by dual immunofluorescence microscopy. T-cell markers were compared with patients’ pathological variables, DNA mismatch repair (MMR) status, and survival using Cox proportional hazards models. FoxP3+ and CD3+ T-cell densities increased in carcinomas compared to autologous normal mucosa (p< 0.0001). An increase in intraepithelial FoxP3+ cells was associated with poor tumor differentiation (p=0.038) and female gender (p=0.028) and advanced age of patients (p=0.042). FoxP3+ cell density was not prognostic, yet patients with tumors with reduced intraepithelial CD3+ T-cell densities had reduced disease-free survival (DFS) times (hazard ratio [HR] 1.87 [1.10, 3.16]; p=0.018). A low intraepithelial CD3+:FoxP3+ cell ratio predicted reduced DFS (46.2% vs. 66.7% survival at 5 years; HR 2.17 [1.11, 4.23]; p= 0.0205). The prognostic impact of these markers was maintained when tumors were stratified by MMR status. By multivariate analysis, a low CD3+:FoxP3+ cell ratio (p=0.0318) and low numbers of CD3+ T cells (p=0.0397) predicted shorter DFS times and were stronger prognostic variables than tumor stage or number of lymph node metastases. A low intraepithelial CD3+:FoxP3+ cell ratio and reduced numbers of CD3+ T cells were associated with reduced patient survival time, indicating the importance of an effector to Treg cell ratio in colon cancer prognosis.
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