Oncotarget

Research Papers:

Parity improves anti-tumor immunity in breast cancer patients

Anna-Lena Krause, Florian Schuetz, Marc Boudewijns, Maria Pritsch, Markus Wallwiener, Michael Golatta, Joachim Rom, Joerg Heil, Christof Sohn, Andreas Schneeweiss, Philipp Beckhove _ and Christoph Domschke

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Oncotarget. 2017; 8:104981-104991. https://doi.org/10.18632/oncotarget.20756

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Abstract

Anna-Lena Krause1, Florian Schuetz2, Marc Boudewijns2, Maria Pritsch1, Markus Wallwiener2, Michael Golatta2, Joachim Rom2, Joerg Heil2, Christof Sohn2, Andreas Schneeweiss2, Philipp Beckhove1,3,* and Christoph Domschke2,*

1Translational Immunology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Department of Gynecology and Obstetrics, Heidelberg University Hospital, National Center for Tumor Diseases (NCT), Heidelberg, Germany

3Regensburg Center for Interventional Immunology (RCI) and University Medical Center of Regensburg, Regensburg, Germany

*Equal contributions

Correspondence to:

Philipp Beckhove, email: beckhove@rcii.de

Christoph Domschke, email: christoph.domschke@med.uni-heidelberg.de

Keywords: pregnancy; breast cancer; anti-tumor T cells; regulatory T cells; tumor-associated antigens

Received: July 08, 2017     Accepted: August 04, 2017     Published: September 08, 2017

ABSTRACT

Compared to nulliparous women, parous women have an up to 50% lower lifetime risk of developing breast cancer. An endogenous mechanism to prevent the development of cancer is the destruction of tumor cells by T cells that recognize tumor-associated antigens (TAA). Since a number of TAA are also highly present in the breast and placenta of pregnant women, we investigated the induction and characteristics of spontaneous T cell responses against TAA during pregnancy.

To this end, we collected peripheral blood from healthy nulliparous, primigravid and parous women, as well as from breast cancer patients. IFN-γ ELISpot assays were performed to measure the intensity and specificity of T cell responses against 11 different TAA. The impact of TAA-specific Treg cells on anti-TAA responses was assessed by performing the assay before and after depletion of CD4+CD25+ T cells. The antigenic specificities of these Treg cells were analyzed by the Treg specificity assay. Furthermore, we conducted flow cytometric analyses to determine the memory phenotype and cytokine secretion profile of TAA-specific T cells.

Our results demonstrate that pregnancy induces functional and long-lived memory and effector T cells that react against multiple TAA. These persist for many decades in parous females, but are not found in age-matched females without children. We also detected TAA-specific Treg cells, which suppressed strong effector T cell responses after delivery. Nulliparous breast cancer patients displayed median TAA-specific effector T cell responses to be decreased threefold compared to parous patients, which could be restored in vitro after depletion of Treg cells.


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