FOXP3+ Regulatory T Cells and Tumoral Indoleamine 2,3-Dioxygenase Expression Predicts the Carcinogenesis of Intraductal Papillary Mucinous Neoplasms of the Pancreas
FOXP3+ Regulatory T Cells and Tumoral Indoleamine 2,3-Dioxygenase Expression Predicts the Carcinogenesis of Intraductal Papillary Mucinous Neoplasms of the Pancreas
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DOI：
10.1159/000308966
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发表时间：
2010-01-01
期刊：
影响因子：
3.6
通讯作者：
Nakajima, Atsushi
中科院分区：
文献类型：
--
作者：
Kobayashi, Noritoshi;Kubota, Kensuke;Nakajima, Atsushi
背景与目的：FOXP3+调节性T细胞（Tregs）在自我耐受和抑制有效的抗肿瘤免疫反应中发挥核心作用。最近的一项研究表明，吲哚胺2,3-双加氧酶（IDO）介导的色氨酸耗竭能够影响局部肿瘤浸润淋巴细胞。本研究的目的是探讨胰腺导管内乳头状粘液瘤（IPMNs）进展过程中肿瘤浸润Tregs和肿瘤IDO表达的临床意义。方法：应用免疫组化方法研究IPMNs组织中FOXP3+ Tregs、CD8+淋巴细胞及IDO的表达。我们招募了39例IPMNs患者（IPMA：腺瘤，n = 11； IPMB：交界性恶性，n = 9； IPMC：非侵袭性癌，n = 7； I-IPMC：侵袭性IPMC， n = 12）。结果：在IPMNs的癌变过程中，Tregs的患病率逐渐升高（Kruskal-Wallis检验：p < 0.0001）。5例IPMNs患者（IPMC, n = 1; I-IPMC, n = 4）观察肿瘤中IDO的表达。IDO在肿瘤中的表达与IPMNs中Tregs的患病率呈正相关。结论：FOXP3+ Tregs在恶性肿瘤前期对IPMNs的免疫监视中起调控作用。IDO在肿瘤中的表达是IPMNs多阶段癌变的晚期现象之一。版权所有：S. Karger AG, Basel and IAP
Background and Aims: FOXP3+ regulatory T cells (Tregs) play a central role in self-tolerance and suppress the effective antitumor immune response. A recent study revealed that indoleamine 2,3-dioxygenase (IDO)-mediated tryptophan depletion was able to affect local tumor-infiltrating lymphocytes. The aim of this study was to investigate the clinical significance of the tumor-infiltrating Tregs and tumoral IDO expression during the progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Methods: We investigated the prevalence and localization of FOXP3+ Tregs, CD8+ lymphocytes, and IDO expression in IPMNs by immunohistochemistry. We recruited 39 cases with IPMNs (IPMA: adenoma, n = 11; IPMB: borderline malignancy, n = 9; IPMC: noninvasive carcinoma, n = 7; I-IPMC: invasive IPMC, n = 12). Results: The prevalence of Tregs increased step by step during the carcinogenesis of IPMNs (Kruskal-Wallis test: p < 0.0001). IDO expression in the tumor was observed in 5 cases with IPMNs (IPMC, n = 1; I-IPMC, n = 4). IDO expression in the tumor was positively correlated with the prevalence of Tregs in IPMNs. Conclusions: FOXP3+ Tregs play a role in controlling the immune surveillance against IPMNs at the premalignant stage. IDO expression in the tumor is one of the late-stage phenomena of multistage carcinogenesis of IPMNs. Copyright (C) 2010 S. Karger AG, Basel and IAP