The composition of T cell infiltrates varies in primary invasive breast cancer of different molecular subtypes as well as according to tumor size and nodal status

Virchows Arch. 2019 Jul;475(1):13-23. doi: 10.1007/s00428-019-02568-y. Epub 2019 Apr 17.

Abstract

T lymphocytes are the most numerous immune cells in tumor-associated infiltrates and include several subpopulations of either anticancer or pro-tumorigenic functions. However, the associations between levels of different T cell subsets and breast cancer molecular subtypes as well as other prognostic factors have not been fully established yet. We performed immunohistochemistry for CD8 (cytotoxic T cells (CTL)), FOXP3 (regulatory T cells (Tregs)), and GATA3 (Th2 cells) in 106 formalin-fixed paraffin-embedded invasive breast cancer tissue samples and analyzed both the numbers and percentages of investigated cells in tumor-associated infiltrates. We observed that triple-negative breast cancer (TNBC) and HER2+ non-luminal breast tumors were associated with more numerous CTLs and Tregs and a higher Treg/Th2 cell ratio as compared with luminal A subtype. A higher Treg percentage was related to a decreased hormone receptor expression, an increase in the Ki67 level, a greater tumor size of luminal tumors, and the presence of lymph node metastases. Moreover, differences in the composition of T cell infiltrates were associated with HER2 status and histologic grade and type, and a distinct immune pattern was observed in tumors of different phenotypes regarding pT stage and nodal status. The results of our work show the diversity of T cell infiltrates in primary invasive breast cancers of different phenotypes and suggest that progression of luminal or non-luminal tumors is related to distinct tumor-associated T cell composition.

Keywords: Breast cancer; Cytotoxic T cells; Microenvironment; Regulatory T cells; Th2 cells; Tumor-infiltrating lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Female
  • Forkhead Transcription Factors / analysis
  • GATA3 Transcription Factor / analysis
  • Humans
  • Immunohistochemistry
  • Immunophenotyping / methods
  • Ki-67 Antigen / analysis
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Phenotype
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Th2 Cells / immunology
  • Tumor Burden
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Ki-67 Antigen
  • MKI67 protein, human