Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer

J Immunol. 2012 Nov 15;189(10):5029-36. doi: 10.4049/jimmunol.1201892. Epub 2012 Oct 3.

Abstract

Understanding and dissecting the role of different subsets of regulatory tumor-infiltrating lymphocytes (TILs) in the immunopathogenesis of individual cancer is a challenge for anti-tumor immunotherapy. High levels of γδ regulatory T cells have been discovered in breast TILs. However, the clinical relevance of these intratumoral γδ T cells is unknown. In this study, γδ T cell populations were analyzed by performing immunohistochemical staining in primary breast cancer tissues from patients with different stages of cancer progression. Retrospective multivariate analyses of the correlations between γδ T cell levels and other prognostic factors and clinical outcomes were completed. We found that γδ T cell infiltration and accumulation in breast tumor sites was a general feature in breast cancer patients. Intratumoral γδ T cell numbers were positively correlated with advanced tumor stages, HER2 expression status, and high lymph node metastasis but inversely correlated with relapse-free survival and overall survival of breast cancer patients. Multivariate and univariate analyses of tumor-infiltrating γδ T cells and other prognostic factors further suggested that intratumoral γδ T cells represented the most significant independent prognostic factor for assessing severity of breast cancer compared with the other known factors. Intratumoral γδ T cells were positively correlated with FOXP3(+) cells and CD4(+) T cells but negatively correlated with CD8(+) T cells in breast cancer tissues. These findings suggest that intratumoral γδ T cells may serve as a valuable and independent prognostic biomarker, as well as a potential therapeutic target for human breast cancer.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Movement / immunology*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Immunotherapy
  • Middle Aged
  • Neoplasm Staging
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Survival Rate
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology

Substances

  • Biomarkers
  • Receptors, Antigen, T-Cell, gamma-delta