Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients

Breast Cancer Res Treat. 2017 Jan;161(1):51-62. doi: 10.1007/s10549-016-4037-z. Epub 2016 Oct 27.


Purpose: Breast cancer is a leading cause of cancer deaths in women, but despite steady improvements in therapies, treatment is still suboptimal. Immunotherapy holds promise as a more effective therapy for breast cancer; supporting this, our prior study showed that patients possessing HER2-reactive CD8+ T cells in blood experience survival superior to patients without these cells. Here, we define a composite set of biomarkers that identify patients with T cell responses to tumour antigens.

Methods: We assessed T cell responses following in vitro stimulation with the HER2, MUC1 and SUR tumour-associated antigens (TAA) by flow cytometry and intracellular cytokine staining in 50 breast cancer patients. We also measured HLA type, serum cytokines, tumour-infiltrating leukocytes and blood leukocyte populations.

Results: We found few correlations between TAA-reactive T cells and HLA type, serum cytokines and tumour-infiltrating leukocytes, whereas blood leukocyte phenotypes broadly correlated with TAA responses. This showed monocytes, natural killer cells, dendritic cells and T cells to be inversely associated with both CD4+ and CD8+ T cells reactive to tumour antigens. Moreover, combining multiple parameters improved the accuracy in predicting patients with TAA-responsive T cells.

Conclusion: This study therefore defines composite immune profiles that identify patients responding to TAAs which may allow better personalisation of cancer therapies.

Keywords: Blood leukocytes; Breast cancer; HER2; MUC1; Survivin; Tumour-associated antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology*
  • Biomarkers
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Cytokines / blood
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Immunogenetic Phenomena*
  • Immunophenotyping
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Middle Aged
  • Mucin-1 / genetics
  • Mucin-1 / metabolism
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Neoplasm Grading
  • Neoplasm Staging
  • Phenotype
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*


  • Antigens, Neoplasm
  • Biomarkers
  • Cytokines
  • HLA Antigens
  • Mucin-1
  • Receptor, ErbB-2