Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer

Seung Tae Kim, Hoiseon Jeong, Ok Hee Woo, Jae Hong Seo, Aeree Kim, Eun Sook Lee, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Kyong Hwa Park

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57 Citations (Scopus)

Abstract

BACKGROUND:: The balance in the immune system between immune surveillance against non-self-antigens and tolerance of self-antigens is known to be associated with the prognosis of breast cancer patients. However, immunologic signals in tumor microenvironment according to biological characteristics of cancer cells have not been clearly elucidated. CD4 T cells, CD8 T cells, and forkhead box P3-positive (Foxp3) regulatory T cells (Tregs) are the main keys for immune surveillance and tolerance, respectively. We evaluated the correlations between the immunologic balance and tumor characteristics and their impact on recurrence. PATIENTS AND METHODS:: CD8 T cells and Foxp3 Tregs were detected by immunohistochemistry using the paraffin-embedded tumor samples from the 72 patients with early stage (I to III) breast cancer. Clinicopathologic data including tumor size and grade, lymph node metastasis, stage, patient's age, expression status of estrogen receptor (ER), progesterone receptor, p53, Ki-67, and human epidermal growth factor receptor-2/neu, and recurrence were reviewed. RESULTS:: The decreased number of CD8 T cells was significantly associated with tumors with lymph node metastasis (P=0.027), higher stage (stage III, P=0.013), and immunopositivity of Ki-67 (P=0.026). In contrast, the increased number of Foxp3 Tregs was significantly correlated with tumors with lymph node metastasis (P=0.027), immunopositivity for p53 (P=0.026), and positive for Ki-67 (P<0.001). There were significant correlations between the increased Foxp3 Treg/CD4 T-cell ratio and lymph node metastasis (P=0.011), the expression of ER (P=0.023), and immunopositivity of p53 (P=0.031) and Ki-67 (P= 0.003). Of note, lower Foxp3 Treg/CD4 T-cell ratio was significantly associated with triple-negative breast cancer (P=0.004). Disease-free survival of analyzed patients was significantly associated with the number of Foxp3 Tregs (dichotomized by a cutoff point of 17, P= 0.014) only. Univariate analysis indicated that tumor grade (P=0.017), the expression of ER (P=0.032), and non-triple-negative breast cancer (P=0.022) were independent prognostic factors for disease-free survival. CONCLUSIONS:: Our data showed that lymph node metastases, immunopositivity of p53 and Ki67, and non-triple-negative tumors were associated with high regulatory T-cell infiltration. The role of immunologic balance as a prognostic marker for recurrence must be evaluated more clearly in the future study.

Original languageEnglish
Pages (from-to)224-231
Number of pages8
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume36
Issue number3
DOIs
Publication statusPublished - 2013 Jun 1

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Tumor-Infiltrating Lymphocytes
Breast Neoplasms
Recurrence
T-Lymphocytes
Lymph Nodes
Neoplasm Metastasis
Neoplasms
Estrogen Receptors
Regulatory T-Lymphocytes
Disease-Free Survival
Triple Negative Breast Neoplasms
Immune Tolerance
Tumor Microenvironment
Autoantigens
Progesterone Receptors
Paraffin
Immune System
Immunohistochemistry
Antigens

Keywords

  • CD8+ T cell
  • early breast cancer
  • Foxp3+ Treg

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{3b8ed4d278484358b79d943607d1cd0e,
title = "Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer",
abstract = "BACKGROUND:: The balance in the immune system between immune surveillance against non-self-antigens and tolerance of self-antigens is known to be associated with the prognosis of breast cancer patients. However, immunologic signals in tumor microenvironment according to biological characteristics of cancer cells have not been clearly elucidated. CD4 T cells, CD8 T cells, and forkhead box P3-positive (Foxp3) regulatory T cells (Tregs) are the main keys for immune surveillance and tolerance, respectively. We evaluated the correlations between the immunologic balance and tumor characteristics and their impact on recurrence. PATIENTS AND METHODS:: CD8 T cells and Foxp3 Tregs were detected by immunohistochemistry using the paraffin-embedded tumor samples from the 72 patients with early stage (I to III) breast cancer. Clinicopathologic data including tumor size and grade, lymph node metastasis, stage, patient's age, expression status of estrogen receptor (ER), progesterone receptor, p53, Ki-67, and human epidermal growth factor receptor-2/neu, and recurrence were reviewed. RESULTS:: The decreased number of CD8 T cells was significantly associated with tumors with lymph node metastasis (P=0.027), higher stage (stage III, P=0.013), and immunopositivity of Ki-67 (P=0.026). In contrast, the increased number of Foxp3 Tregs was significantly correlated with tumors with lymph node metastasis (P=0.027), immunopositivity for p53 (P=0.026), and positive for Ki-67 (P<0.001). There were significant correlations between the increased Foxp3 Treg/CD4 T-cell ratio and lymph node metastasis (P=0.011), the expression of ER (P=0.023), and immunopositivity of p53 (P=0.031) and Ki-67 (P= 0.003). Of note, lower Foxp3 Treg/CD4 T-cell ratio was significantly associated with triple-negative breast cancer (P=0.004). Disease-free survival of analyzed patients was significantly associated with the number of Foxp3 Tregs (dichotomized by a cutoff point of 17, P= 0.014) only. Univariate analysis indicated that tumor grade (P=0.017), the expression of ER (P=0.032), and non-triple-negative breast cancer (P=0.022) were independent prognostic factors for disease-free survival. CONCLUSIONS:: Our data showed that lymph node metastases, immunopositivity of p53 and Ki67, and non-triple-negative tumors were associated with high regulatory T-cell infiltration. The role of immunologic balance as a prognostic marker for recurrence must be evaluated more clearly in the future study.",
keywords = "CD8+ T cell, early breast cancer, Foxp3+ Treg",
author = "Kim, {Seung Tae} and Hoiseon Jeong and Woo, {Ok Hee} and Seo, {Jae Hong} and Aeree Kim and Lee, {Eun Sook} and Shin, {Sang Won} and Kim, {Yeul Hong} and Kim, {Jun Suk} and Park, {Kyong Hwa}",
year = "2013",
month = "6",
day = "1",
doi = "10.1097/COC.0b013e3182467d90",
language = "English",
volume = "36",
pages = "224--231",
journal = "American Journal of Clinical Oncology",
issn = "0277-3732",
publisher = "Lippincott Williams and Wilkins",
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}

TY - JOUR

T1 - Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer

AU - Kim, Seung Tae

AU - Jeong, Hoiseon

AU - Woo, Ok Hee

AU - Seo, Jae Hong

AU - Kim, Aeree

AU - Lee, Eun Sook

AU - Shin, Sang Won

AU - Kim, Yeul Hong

AU - Kim, Jun Suk

AU - Park, Kyong Hwa

PY - 2013/6/1

Y1 - 2013/6/1

N2 - BACKGROUND:: The balance in the immune system between immune surveillance against non-self-antigens and tolerance of self-antigens is known to be associated with the prognosis of breast cancer patients. However, immunologic signals in tumor microenvironment according to biological characteristics of cancer cells have not been clearly elucidated. CD4 T cells, CD8 T cells, and forkhead box P3-positive (Foxp3) regulatory T cells (Tregs) are the main keys for immune surveillance and tolerance, respectively. We evaluated the correlations between the immunologic balance and tumor characteristics and their impact on recurrence. PATIENTS AND METHODS:: CD8 T cells and Foxp3 Tregs were detected by immunohistochemistry using the paraffin-embedded tumor samples from the 72 patients with early stage (I to III) breast cancer. Clinicopathologic data including tumor size and grade, lymph node metastasis, stage, patient's age, expression status of estrogen receptor (ER), progesterone receptor, p53, Ki-67, and human epidermal growth factor receptor-2/neu, and recurrence were reviewed. RESULTS:: The decreased number of CD8 T cells was significantly associated with tumors with lymph node metastasis (P=0.027), higher stage (stage III, P=0.013), and immunopositivity of Ki-67 (P=0.026). In contrast, the increased number of Foxp3 Tregs was significantly correlated with tumors with lymph node metastasis (P=0.027), immunopositivity for p53 (P=0.026), and positive for Ki-67 (P<0.001). There were significant correlations between the increased Foxp3 Treg/CD4 T-cell ratio and lymph node metastasis (P=0.011), the expression of ER (P=0.023), and immunopositivity of p53 (P=0.031) and Ki-67 (P= 0.003). Of note, lower Foxp3 Treg/CD4 T-cell ratio was significantly associated with triple-negative breast cancer (P=0.004). Disease-free survival of analyzed patients was significantly associated with the number of Foxp3 Tregs (dichotomized by a cutoff point of 17, P= 0.014) only. Univariate analysis indicated that tumor grade (P=0.017), the expression of ER (P=0.032), and non-triple-negative breast cancer (P=0.022) were independent prognostic factors for disease-free survival. CONCLUSIONS:: Our data showed that lymph node metastases, immunopositivity of p53 and Ki67, and non-triple-negative tumors were associated with high regulatory T-cell infiltration. The role of immunologic balance as a prognostic marker for recurrence must be evaluated more clearly in the future study.

AB - BACKGROUND:: The balance in the immune system between immune surveillance against non-self-antigens and tolerance of self-antigens is known to be associated with the prognosis of breast cancer patients. However, immunologic signals in tumor microenvironment according to biological characteristics of cancer cells have not been clearly elucidated. CD4 T cells, CD8 T cells, and forkhead box P3-positive (Foxp3) regulatory T cells (Tregs) are the main keys for immune surveillance and tolerance, respectively. We evaluated the correlations between the immunologic balance and tumor characteristics and their impact on recurrence. PATIENTS AND METHODS:: CD8 T cells and Foxp3 Tregs were detected by immunohistochemistry using the paraffin-embedded tumor samples from the 72 patients with early stage (I to III) breast cancer. Clinicopathologic data including tumor size and grade, lymph node metastasis, stage, patient's age, expression status of estrogen receptor (ER), progesterone receptor, p53, Ki-67, and human epidermal growth factor receptor-2/neu, and recurrence were reviewed. RESULTS:: The decreased number of CD8 T cells was significantly associated with tumors with lymph node metastasis (P=0.027), higher stage (stage III, P=0.013), and immunopositivity of Ki-67 (P=0.026). In contrast, the increased number of Foxp3 Tregs was significantly correlated with tumors with lymph node metastasis (P=0.027), immunopositivity for p53 (P=0.026), and positive for Ki-67 (P<0.001). There were significant correlations between the increased Foxp3 Treg/CD4 T-cell ratio and lymph node metastasis (P=0.011), the expression of ER (P=0.023), and immunopositivity of p53 (P=0.031) and Ki-67 (P= 0.003). Of note, lower Foxp3 Treg/CD4 T-cell ratio was significantly associated with triple-negative breast cancer (P=0.004). Disease-free survival of analyzed patients was significantly associated with the number of Foxp3 Tregs (dichotomized by a cutoff point of 17, P= 0.014) only. Univariate analysis indicated that tumor grade (P=0.017), the expression of ER (P=0.032), and non-triple-negative breast cancer (P=0.022) were independent prognostic factors for disease-free survival. CONCLUSIONS:: Our data showed that lymph node metastases, immunopositivity of p53 and Ki67, and non-triple-negative tumors were associated with high regulatory T-cell infiltration. The role of immunologic balance as a prognostic marker for recurrence must be evaluated more clearly in the future study.

KW - CD8+ T cell

KW - early breast cancer

KW - Foxp3+ Treg

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