title: 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.
abstract: 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.
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: K
authors.initials: K
authors.lastname: Yoshimura
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Kuramasu
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: R
authors.initials: R
authors.lastname: Kamei
authors.forename: R
authors.initials: R
authors.lastname: Tsunedomi
authors.forename: Y
authors.initials: Y
authors.lastname: Shindo
authors.forename: M
authors.initials: M
authors.lastname: Inui
authors.forename: K
authors.initials: K
authors.lastname: Tamada
authors.forename: S
authors.initials: S
authors.lastname: Yoshino
authors.forename: S
authors.initials: S
authors.lastname: Hazama
authors.forename: M
authors.initials: M
authors.lastname: Oka
mesh_terms: D060887:B7 Antigens / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry; D047368:Tumor Burden; D019139:Tumor Escape; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D060887:B7 Antigens; D051858:Forkhead Transcription Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; C423237:CD276 protein, human; C418974:FOXP3 protein, human; C508053:ERBB2 protein, human