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

• Published in: Annals of surgical oncology Vol. 21; no. Suppl 4; pp. 546 - 554
• Main Authors: Maeda, N., Yoshimura, K., Yamamoto, S., Kuramasu, A., Inoue, M., Suzuki, N., Watanabe, Y., Maeda, Y., Kamei, R., Tsunedomi, R., Shindo, Y., Inui, M., Tamada, K., Yoshino, S., Hazama, S., Oka, M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-12-2014; Springer Nature B.V
• Subjects: 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; Medicine; Medicine & Public Health; Middle Aged; Oncology; Receptor, ErbB-2 - analysis; Surgery; Surgical Oncology; Survival Rate; T-Lymphocytes, Regulatory - chemistry; Translational Research and Biomarkers; Tumor Burden; Tumor Escape; Tumor Microenvironment - immunology; Foxp3 Expression; Breast Cancer Patient; Tumor Immune Evasion; Breast Cancer; Overall Survival
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-014-3564-2

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.