Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients

Ann Surg Oncol. 2014 Dec;21 Suppl 4(Suppl 4):S546-54. doi: 10.1245/s10434-014-3564-2. Epub 2014 Feb 22.


Background: In the tumor microenvironment, factors inhibiting the targeting of cancer cells by activated T cells have recently been noted. B7-H3 belongs to the B7 superfamily of immune regulatory ligands and plays an important role in the adaptive immune response of co-inhibitory/stimulatory factors in regulating T cells. However, the degree to which B7-H3 directly affects tumor immune evasion mechanisms remains unclear, particularly in patients with breast cancer. Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The present study demonstrated that expression of B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment independently affected prognosis in breast cancer patients.

Methods: We immunohistochemically investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in pathological specimens from 90 patients with breast cancer.

Results: Positive B7-H3 expression was associated with shorter recurrence-free survival (RFS) (p = 0.014). A higher percentage of Foxp3-positive cells also correlated with shorter RFS (p = 0.039). Multivariate analysis showed B7-H3 as an independent factor on RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated significantly with larger tumor size (>2 cm), expression of human epidermal growth factor receptor 2 (HER2), and higher nuclear grade (p = 0.003, p < 0.001, p = 0.001, respectively). No correlation was identified between expression of B7-H3 and the percentage of Foxp3-positive TILs.

Conclusions: B7-H3 and Foxp3 can be regarded as markers of poor prognosis in breast cancer. These expressions were not correlated, suggesting that B7-H3 expression plays an independent role in tumor immune evasion, regardless of Tregs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7 Antigens / analysis*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / chemistry*
  • Carcinoma, Ductal, Breast / immunology
  • Carcinoma, Ductal, Breast / pathology
  • Disease-Free Survival
  • Female
  • Forkhead Transcription Factors / analysis
  • Humans
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating* / chemistry
  • Middle Aged
  • Receptor, ErbB-2 / analysis
  • Survival Rate
  • T-Lymphocytes, Regulatory* / chemistry
  • Tumor Burden
  • Tumor Escape*
  • Tumor Microenvironment / immunology


  • B7 Antigens
  • CD276 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • ERBB2 protein, human
  • Receptor, ErbB-2