CD8 T Cell Score as a Prognostic Biomarker for Triple Negative Breast Cancer

Int J Mol Sci. 2020 Sep 22;21(18):6968. doi: 10.3390/ijms21186968.

Abstract

CD8 T cell is an essential component of tumor-infiltrating lymphocytes (TIL) and tumor immune microenvironment (TIME). Using the xCell CD8 T cell score of whole tumor gene expression data, we estimated these cells in total of 3837 breast cancer patients from TCGA, METABRIC and various GEO cohorts. The CD8 score correlated strongly with expression of CD8 genes. The score was highest for triple-negative breast cancer (TNBC), and a high score was associated with high tumor immune cytolytic activity and better survival in TNBC but not other breast cancer subtypes. In TNBC, tumors with a high CD8 score had enriched expression of interferon (IFN)-α and IFN-γ response and allograft rejection gene sets, and greater infiltration of anti-cancerous immune cells. The score strongly correlated with CD4 memory T cells in TNBC, and tumors with both a high CD8 score and high CD4 memory T cell abundance had significantly better survival. Finally, a high CD8 score was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, a high CD8 T cell score is associated with better survival in TNBC, particularly when tumor CD4 memory T cells were elevated. Our findings also suggest a possible use of the score as a predictive biomarker for response to immune checkpoint therapy.

Keywords: CD4 memory T cells; CD8 T cells; biomarker; cytolytic activity; immune cell; survival analysis; triple negative breast cancer; tumor immune microenvironment; tumor infiltrating lymphocyte; xCell.

MeSH terms

  • Biomarkers, Tumor / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / pathology
  • Databases, Nucleic Acid*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Immunologic Memory
  • Interferon-alpha / immunology*
  • Interferon-gamma / immunology*
  • Neoplasm Proteins / immunology*
  • Survival Rate
  • Triple Negative Breast Neoplasms* / immunology
  • Triple Negative Breast Neoplasms* / mortality
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • IFNG protein, human
  • Interferon-alpha
  • Neoplasm Proteins
  • Interferon-gamma