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: Article

16 引文 (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English
頁(從 - 到)698-703
頁數6
期刊Oral Oncology
51
發行號7
DOIs
出版狀態Published - 2015 七月 1

指紋

Regulatory T-Lymphocytes
Neoplasms
Squamous Cell Carcinoma
Interleukin-10
Chemokine CCL22
Cytokines
Immunologic Monitoring
Serum
Cellular Immunity
ROC Curve
Immunosuppression
Esophagus
Neck
Cell Count
Biomarkers
Immunohistochemistry
Head

All Science Journal Classification (ASJC) codes

  • Oral Surgery
  • Oncology
  • Cancer Research

引用此文

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title = "Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract",
abstract = "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.",
author = "Wang, {Wen Lun} and Chang, {Wei Lun} and Yang, {Hsiao Bai} and Chang, {I. Wei} and Lee, {Ching Tai} and Chang, {Chi Yang} and Lin, {Jaw Town} and Sheu, {Bor Shyang}",
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Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract. / Wang, Wen Lun; Chang, Wei Lun; Yang, Hsiao Bai; Chang, I. Wei; Lee, Ching Tai; Chang, Chi Yang; Lin, Jaw Town; Sheu, Bor Shyang.

於: Oral Oncology, 卷 51, 編號 7, 01.07.2015, p. 698-703.

研究成果: Article

TY - JOUR

T1 - Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract

AU - Wang, Wen Lun

AU - Chang, Wei Lun

AU - Yang, Hsiao Bai

AU - Chang, I. Wei

AU - Lee, Ching Tai

AU - Chang, Chi Yang

AU - Lin, Jaw Town

AU - Sheu, Bor Shyang

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

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