Low intratumoral regulatory T cells and high peritumoral CD8+ T cells relate to long-term survival in patients with pancreatic ductal adenocarcinoma after pancreatectomy
Low intratumoral regulatory T cells and high peritumoral CD8+ T cells relate to long-term survival in patients with pancreatic ductal adenocarcinoma after pancreatectomy
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DOI：
10.1007/s00262-015-1775-4
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发表时间：
2016-01-01
影响因子：
5.8
通讯作者：
Qin, Xinyu
中科院分区：
文献类型：
--
作者：
Liu, Li;Zhao, Guochao;Qin, Xinyu
胰腺导管腺癌（PDAC）的预后仍然非常差。最近的研究集中在淋巴细胞在PDAC微环境中的作用。本研究采用免疫组织化学方法，探讨了肿瘤微环境中肿瘤内或肿瘤周围CD4（+）Foxp3（+）调节性T细胞（TCRs）和CD8（+）T细胞的临床意义，并分析了它们与92例PDAC患者切除术后预后的关系。CD8（+）T细胞在瘤周部位更常见，而CD4（+）Foxp3（+）T细胞在瘤内区域更常见。两者均未表现出与其他临床病理因素的任何关系。肿瘤内T细胞水平低的患者比肿瘤内T细胞水平高的患者无病生存期长（DFS 22.2 vs. 11.2个月，p < 0.001），肿瘤周围CD8（+）T细胞水平高的患者比肿瘤内T细胞水平低的患者总生存期长（OS 31.0 vs. 14.2个月，p < 0.001）。多变量分析表明，肿瘤内T细胞（风险比，HR 3.39，p = 0.010）和肿瘤周围CD8（+）T细胞（HR 0.10，p < 0.001）分别与DFS和OS相关。这些结果表明，肿瘤内T细胞是DFS的负预测因子，而肿瘤周围CD8（+）T细胞是胰腺切除术后PDAC患者OS的正预测因子。
The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Recent studies have focused on the role of lymphocytes in the PDAC microenvironment. Using immunohistochemistry, our study explored the clinical significance of intratumoral or peritumoral CD4(+)Foxp3(+) regulatory T cells (Tregs) and CD8(+) T cells in the tumor microenvironment and analyzed their relation to the prognosis of PDAC in a consecutive series of 92 patients after resection. CD8(+) T cells were more frequently seen within peritumoral sites, while CD4(+)Foxp3(+) Tregs were more frequent within intratumoral areas. Neither exhibited any relationship with other clinicopathologic factors. Patients with low levels of intratumoral Tregs had longer disease-free survival than those with higher levels (DFS 22.2 vs. 11.2 months, p < 0.001), and patients with higher levels of peritumoral CD8(+) T cells had longer overall survival than those with lower levels (OS 31.0 vs. 14.2 months, p < 0.001). Multivariate analysis demonstrated that intratumoral Tregs (hazard ratio, HR 3.39, p = 0.010) and peritumoral CD8(+) T cells (HR 0.10, p < 0.001) are related to DFS and OS, respectively. These results indicate that intratumoral Tregs are a negative predictor of DFS, while peritumoral CD8(+) T cells are a positive predictor of OS for PDAC patients with pancreatectomy.