Tumor-infiltrating lymphocytes are associated with β-catenin overexpression in breast cancer

Cancer Biomark. 2018 Feb 14;21(3):639-650. doi: 10.3233/CBM-170708.

Abstract

Background: Inhibition of lymphocytes infiltration and activity may impair antitumor immune response and limit treatment responsiveness. Wnt/β-catenin pathway has been suggested to contribute to immune evasion in tumor by suppressing the function of immune cells and excluding T cell infiltration. However, the effects of Wnt/β-catenin on TILs recruitment remain controversial.

Objective: We aimed to investigate whether intratumoral Wnt/β-catenin signaling could affect the lymphocyte infiltration in breast cancer.

Methods: The distribution of stromal TILs, CD8+ and FOXP3+ TIL subsets, and the expression of β-catenin were separately assessed on consecutive sections of 96 breast cancer specimens.

Results: Both stromal infiltrated TILs and β-catenin expression were upregulated in hormone receptor negative HER2-enriched and TNBC subtypes. Furthermore, high levels of stromal TILs as well as CD8+ or FOXP3+ TIL subsets were associated with β-catenin overexpression by breast cancer, respectively.

Conclusions: For the first time, we demonstrated that rather than excluding lymphocytes infiltration as reported in mela-noma, high levels of TILs were associated with β-catenin overexpression in BC. Wnt/β-catenin signaling may play a critical role in BC immunity, particularly in HER2-enriched and triple negative BC, and may serve as a potential target for regulating immune infiltrates in breast cancer.

Keywords: CD8+ TILs; FOXP3+ TILs; Tumor infiltrating lymphocytes; Wnt/β-catenin signaling; breast cancer.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Tumor Burden
  • Tumor Microenvironment
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • Biomarkers
  • beta Catenin