4.7 Article

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

Journal

Publisher

MDPI
DOI: 10.3390/ijms21186968

Keywords

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

Funding

  1. National Institutes of Health, USA [R01CA160688]
  2. Edward K. Duch Foundation
  3. National Cancer Institute, USA [P30-CA016056]
  4. [19H03714]
  5. [18K19576]

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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)-alpha and IFN-gamma 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.

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