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CD14+ HLA-DR−/low MDSCs are elevated in the periphery of early-stage breast cancer patients and suppress autologous T cell proliferation

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Abstract

Purpose

Despite the recent expansion in the use of immunotherapy for many cancer types, it is still not a standard treatment for breast cancer. Identifying differences in the immune systems of breast cancer patients compared to healthy women might provide insight into potential targets for immunotherapy and thus may assist its clinical implementation.

Methods

Multi-colour flow cytometry was used to investigate myeloid and lymphoid populations in the peripheral blood of breast cancer patients (n = 40) and in the blood of healthy age-matched women (n = 25). We additionally performed functional testing to identify immune suppressive mechanisms used by circulating CD14+ myeloid cells from breast cancer patients.

Results

Our results show that breast cancer patients have significantly elevated frequencies of cells with the monocytic myeloid-derived suppressor cell (mMDSC) phenotype CD14+ HLA-DR−/low compared with healthy women (p < 0.01). We also observed higher levels of earlier differentiated T cells and correspondingly lower levels of T cells in later stages of differentiation (p < 0.05). These disease-associated differences could already be detected in early-stage breast cancer patients in stages 1 and 2 (n = 33 of 40) (p < 0.05). Levels of circulating T cells correlated with certain clinical features and with patient age (p < 0.05). Functional tests showed that CD14+ myeloid cells from breast cancer patients more potently suppressed autologous T cell proliferation than CD14+ cells from healthy women (p < 0.01). Subsequent investigation determined that suppression was mediated in part by reactive oxygen species, because inhibiting this pathway partially restored T cell proliferation (p < 0.01).

Conclusion

Our results highlight the potential importance of cells with mMDSC phenotypes in breast cancer, identifiable already at early stages of disease. This may provide a basis for identifying possible new therapeutic targets to enhance anti-cancer immunity.

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Acknowledgements

This work was supported by a grant from the German Research Foundation (DFG Pa 361/22-1).

Author information

Author notes

  1. Jithendra Kini Bailur

    Present address: Yale Cancer Center, Yale University School of Medicine, 333 Cedar St, New Haven, USA

  2. Christopher Shipp

    Present address: Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Markwiesenstraße 55, 72770, Reutlingen, Germany

Authors and Affiliations

  1. Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestraße 22, 72072, Tübingen, Germany

    Lisa Speigl, Jithendra Kini Bailur, Nicole Janssen, Graham Pawelec & Christopher Shipp

  2. Department of Obstetrics and Gynecology, University Hospital Tübingen, Calwerstraße 7, 72076, Tübingen, Germany

    Helen Burow & Christina-Barbara Walter

  3. John van Geest Cancer Research Centre, Nottingham Trent University, College Dr, Clifton, Nottingham, NG11 8NS, UK

    Graham Pawelec

  4. Division of Cancer Studies, King’s College London, Strand, London, WC2R 2LS, UK

    Graham Pawelec

  5. Health Sciences North Research Institute, 41 Ramsey Lake Road, Sudbury, ON, Canada

    Graham Pawelec

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  1. Lisa Speigl
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Speigl, L., Burow, H., Bailur, J.K. et al. CD14+ HLA-DR−/low MDSCs are elevated in the periphery of early-stage breast cancer patients and suppress autologous T cell proliferation. Breast Cancer Res Treat 168, 401–411 (2018). https://doi.org/10.1007/s10549-017-4594-9

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