Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract

Wen Lun Wang, Wei Lun Chang, Hsiao Bai Yang, I. Wei Chang, Ching Tai Lee, Chi Yang Chang, Jaw Town Lin, Bor Shyang Sheu

研究成果: 雜誌貢獻文章同行評審

21 引文 斯高帕斯(Scopus)

摘要

Objectives Patients with squamous cell carcinomas (SCC) of upper aerodigestive tract, either over head and neck (HNSCC) or esophagus (ESCC), frequently developed synchronous multiple cancers, leading to worse prognosis. This study validated whether suppression of host cancer immunosurveillance mediated by regulatory T cells (Treg) may predispose to the development of synchronous cancers. Methods Tumor tissues of 200 patients (100 ESCC only, 50 HNSCC only, and 50 synchronous SCCs) were quantitatively accessed for the tumor infiltrating Treg by immunohistochemistry. The density of Treg was also correlated to the level of Treg-associated inhibitory cytokines (IL-10, IL-35 and TGF-β1), and chemokine (CCL22). Results The density of tumor infiltrating Treg in the index tumor (i.e. The first malignancy diagnosed) of synchronous SCC group was higher than those of HNSCC or ESCC only (p < 0.05). Selecting the optimal cut-off value of Treg density as 34.6 cells/mm2 by ROC curve, an increased Treg density of the index tumor can be an independent factor for developing synchronous SCCs (OR: 6.13; 95% CI: 2.84-13.26). The Treg density was positively correlated with serum IL-10 level and the degree of CCL22-positive cells infiltration in tumor. Furthermore, the serum inhibitory cytokine IL-10 level was higher in synchronous SCC than in non-synchronous ones (p < 0.001), that indicated the cellular immunosuppression in patients with synchronous cancers. Conclusions A more severe defect in cellular immunity may predispose to multifocal tumor. The Treg cell number in SCC may serve as a novel predictive biomarker for the risk of synchronous cancer development to initiate a proper surveillance program.
原文英語
頁(從 - 到)698-703
頁數6
期刊Oral Oncology
51
發行號7
DOIs
出版狀態已發佈 - 七月 1 2015
對外發佈

ASJC Scopus subject areas

  • 口腔外科
  • 腫瘤科
  • 癌症研究

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