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

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

Author information

1
Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany.
2
Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
3
Pathology Department, Saint Savas Cancer Hospital, Athens, Greece.
4
Histocompatibility & Immunogenetics Lab, Hellenic Cord Blood Bank- H&I Laboratory, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
5
Institute of Cancer Sciences, The University of Manchester, Manchester, M20 4BX, UK.
6
School of Science and Technology, College of Arts and Science, Nottingham Trent University, Burton St, Nottingham, NG1 4BU, UK.
7
Department of Haematological Medicine, The Rayne Institute, King's College London, London, UK.
8
Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany. mrchristophershipp@gmail.com.

Abstract

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

PMID:
27787640
DOI:
10.1007/s10549-016-4037-z
[Indexed for MEDLINE]

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