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01-01-2017 | Clinical trial

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

Authors: Nicole Janssen, Sotirios P. Fortis, Lisa Speigl, Christoforos Haritos, Nectaria N. Sotiriadou, Michael Sofopoulos, Niki Arnogiannaki, Catherine Stavropoulos-Giokas, Amalia Dinou, Sonia Perez, Graham Pawelec, Constantin N. Baxevanis, Christopher Shipp

Published in: Breast Cancer Research and Treatment | Issue 1/2017

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.

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Title: Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients
Authors: Nicole Janssen
Sotirios P. Fortis
Lisa Speigl
Christoforos Haritos
Nectaria N. Sotiriadou
Michael Sofopoulos
Niki Arnogiannaki
Catherine Stavropoulos-Giokas
Amalia Dinou
Sonia Perez
Graham Pawelec
Constantin N. Baxevanis
Christopher Shipp
Publication date: 01-01-2017
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-016-4037-z

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Purpose

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