Immunofluorescence-detected infiltration of CD4 +FOXP3 + regulatory T cells is relevant to the prognosis of patients with endometrial cancer

Wataru Yamagami, Nobuyuki Susumu, Hideo Tanaka, Akira Hirasawa, Kouji Banno, Nao Suzuki, Hiroshi Tsuda, Katsumi Tsukazaki, Daisuke Aoki

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8 + cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients. Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4 +FOXP3 + cells were identified as Tregs in this study. The numbers of CD8 + cells, CD4 +cells, and Tregs as well as the Treg/CD8 + and Treg/CD4 + ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis. Results: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8 + and CD4 + cell counts, Treg count, and Treg/CD8 + and Treg/CD4 + ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8 + ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8 + ratios (P < 0.05). Conclusions: The Treg count and Treg/CD8 + ratio may be new prognostic factors for endometrial cancer.

Original languageEnglish
Pages (from-to)1628-1634
Number of pages7
JournalInternational Journal of Gynecological Cancer
Volume21
Issue number9
DOIs
Publication statusPublished - Dec 1 2011
Externally publishedYes

Fingerprint

Regulatory T-Lymphocytes
Endometrial Neoplasms
Fluorescent Antibody Technique
CD4-CD8 Ratio
Neoplasms
Antibody Binding Sites
Carcinoma
Immune Tolerance
Antibodies
Cytotoxic T-Lymphocytes
Cellular Structures
CD4 Lymphocyte Count
Paraffin
Formaldehyde
Disease-Free Survival
Uterus
Cell Count
Fluorescence
Immunohistochemistry

Keywords

  • Cytotoxic T lymphocytes
  • Endometrial cancer
  • FOXP3
  • Regulatory T cells
  • Tumor immunity

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology
  • Medicine(all)

Cite this

Immunofluorescence-detected infiltration of CD4 +FOXP3 + regulatory T cells is relevant to the prognosis of patients with endometrial cancer. / Yamagami, Wataru; Susumu, Nobuyuki; Tanaka, Hideo; Hirasawa, Akira; Banno, Kouji; Suzuki, Nao; Tsuda, Hiroshi; Tsukazaki, Katsumi; Aoki, Daisuke.

In: International Journal of Gynecological Cancer, Vol. 21, No. 9, 01.12.2011, p. 1628-1634.

Research output: Contribution to journalArticle

Yamagami, Wataru ; Susumu, Nobuyuki ; Tanaka, Hideo ; Hirasawa, Akira ; Banno, Kouji ; Suzuki, Nao ; Tsuda, Hiroshi ; Tsukazaki, Katsumi ; Aoki, Daisuke. / Immunofluorescence-detected infiltration of CD4 +FOXP3 + regulatory T cells is relevant to the prognosis of patients with endometrial cancer. In: International Journal of Gynecological Cancer. 2011 ; Vol. 21, No. 9. pp. 1628-1634.
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abstract = "Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8 + cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients. Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4 +FOXP3 + cells were identified as Tregs in this study. The numbers of CD8 + cells, CD4 +cells, and Tregs as well as the Treg/CD8 + and Treg/CD4 + ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis. Results: Of the 53 patients studied, 50.9{\%} of them had early-stage disease, 49.1{\%} had advanced stage disease, 47.2{\%} had well-differentiated cancer (grade [G] 1), 24.5{\%} had moderately differentiated cancer (G2), and 28.3{\%} had poorly differentiated cancer (G3). The CD8 + and CD4 + cell counts, Treg count, and Treg/CD8 + and Treg/CD4 + ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8 + ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8 + ratios (P < 0.05). Conclusions: The Treg count and Treg/CD8 + ratio may be new prognostic factors for endometrial cancer.",
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AU - Yamagami, Wataru

AU - Susumu, Nobuyuki

AU - Tanaka, Hideo

AU - Hirasawa, Akira

AU - Banno, Kouji

AU - Suzuki, Nao

AU - Tsuda, Hiroshi

AU - Tsukazaki, Katsumi

AU - Aoki, Daisuke

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N2 - Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8 + cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients. Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4 +FOXP3 + cells were identified as Tregs in this study. The numbers of CD8 + cells, CD4 +cells, and Tregs as well as the Treg/CD8 + and Treg/CD4 + ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis. Results: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8 + and CD4 + cell counts, Treg count, and Treg/CD8 + and Treg/CD4 + ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8 + ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8 + ratios (P < 0.05). Conclusions: The Treg count and Treg/CD8 + ratio may be new prognostic factors for endometrial cancer.

AB - Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8 + cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients. Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4 +FOXP3 + cells were identified as Tregs in this study. The numbers of CD8 + cells, CD4 +cells, and Tregs as well as the Treg/CD8 + and Treg/CD4 + ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis. Results: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8 + and CD4 + cell counts, Treg count, and Treg/CD8 + and Treg/CD4 + ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8 + ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8 + ratios (P < 0.05). Conclusions: The Treg count and Treg/CD8 + ratio may be new prognostic factors for endometrial cancer.

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