Parity improves anti-tumor immunity in breast cancer patients.

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

doi:10.18632/oncotarget.20756

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.

Highlights

Parity is associated with a 50% decreased lifetime risk of developing breast cancer [1]
Since T cell immunity plays a major role in breast cancer prognosis, we here studied a potential influence of parity on breast tumor-specific T cell responses
We show that pregnancy induces long-lived memory and regulatory T cell responses against multiple breast cancer-associated antigens that persist for many decades, but are not found in age-matched females without children

Summary

Introduction

Parity is associated with a 50% decreased lifetime risk of developing breast cancer [1]. To date, accumulating evidence supports this concept of “cancer immunosurveillance”: Anti-cancer immune www.impactjournals.com/oncotarget responses are initiated in many breast-, and other cancer patients upon recognition of tumor-associated antigens (TAA) by T lymphocytes [2, 3]. Both the presence of TAA-specific T lymphocytes in the blood [4, 5] and the accumulation of effector and memory T cells [6] correlate with an improved survival of breast cancer patients. The strength of endogenous tumor-specific effector/ memory T cell responses determines the outcome of patients with breast cancer

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Conclusion