%0 Journal Article
%A Ge, Yingzi
%A Böhm, Hans-Henning
%A Rathinasamy, Anchana
%A Xydia, Maria
%A Hu, Xiaoying
%A Pincha, Mudita
%A Umansky, Ludmila
%A Breyer, Christopher
%A Hillier, Michael
%A Bonertz, Andreas
%A Sevko, Alexandra
%A Domschke, Christoph
%A Schuetz, Florian
%A Frebel, Helge
%A Dettling, Steffen
%A Herold-Mende, Christel C
%A Reissfelder, Christoph
%A Weitz, Juergen
%A Umansky, Viktor
%A Beckhove, Philipp
%T Tumor-specific regulatory T cells from the bone marrow orchestrate antitumor immunity in breast cancer.
%J Cancer immunology research
%V 7
%N 12
%@ 2326-6074
%C Philadelphia, Pa.
%I AACR
%M DKFZ-2019-02523
%P 1998-2012
%D 2019
%Z 7(12):1998-2012
%X Endogenous antitumor effector T cell responses and immune suppressive regulatory T cells (Tregs) critically influence the prognosis of cancer patients, yet many of the mechanisms of how this occurs remain unresolved. Based on an analysis of the function, antigen-specificity and distribution of tumor antigen-reactive T cells and Tregs in breast cancer patients and transgenic mouse tumor models we showed that tumor-specific Tregs were selectively activated in the bone marrow (BM) and egressed into the peripheral blood (PB). The BM was constantly depleted of tumor-specific Tregs and was instead a site of increased induction and activity of tumor-reactive effector/memory T cells. Treg egress from the BM was associated with activation-induced expression of peripheral homing receptors such as CCR2. Since breast cancer tissues express the CCR2 ligand CCL2, the activation and egress of tumor antigen-specific Tregs in the BM resulted in the accumulation of Tregs in breast tumor tissue. Such immune-compartmentalization and redistribution of T cell subpopulations between the BM and peripheral tissues was achieved by vaccination with adenoviral vector encoded TRP-2 tumor antigen in a RET transgenic mouse model of spontaneous malignant melanoma. Thus, the BM simultaneously represented a source of tumor-infiltrating Tregs and a site for the induction of endogenous tumor-specific effector T cell responses, suggesting that both antitumor immunity and local immune suppression are orchestrated in the BM.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:31672785
%R 10.1158/2326-6066.CIR-18-0763
%U https://inrepo02.dkfz.de/record/147406