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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)698-703
Number of pages6
JournalOral Oncology
Volume51
Issue number7
DOIs
Publication statusPublished - Jul 1 2015
Externally publishedYes

Fingerprint

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

Keywords

  • Esophageal cancer
  • Head and neck cancer
  • Immunity
  • Regulatory T cell
  • Surveillance
  • Synchronous neoplasm

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

Cite this

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.

In: Oral Oncology, Vol. 51, No. 7, 01.07.2015, p. 698-703.

Research output: Contribution to journalArticle

Wang, Wen Lun ; Chang, Wei Lun ; Yang, Hsiao Bai ; Chang, I. Wei ; Lee, Ching Tai ; Chang, Chi Yang ; Lin, Jaw Town ; Sheu, Bor Shyang. / Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract. In: Oral Oncology. 2015 ; Vol. 51, No. 7. pp. 698-703.
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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.",
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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.

KW - Esophageal cancer

KW - Head and neck cancer

KW - Immunity

KW - Regulatory T cell

KW - Surveillance

KW - Synchronous neoplasm

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