TY  - JOUR
AU  - Ge, Yingzi
AU  - Böhm, Hans-Henning
AU  - Rathinasamy, Anchana
AU  - Xydia, Maria
AU  - Hu, Xiaoying
AU  - Pincha, Mudita
AU  - Umansky, Ludmila
AU  - Breyer, Christopher
AU  - Hillier, Michael
AU  - Bonertz, Andreas
AU  - Sevko, Alexandra
AU  - Domschke, Christoph
AU  - Schuetz, Florian
AU  - Frebel, Helge
AU  - Dettling, Steffen
AU  - Herold-Mende, Christel C
AU  - Reissfelder, Christoph
AU  - Weitz, Juergen
AU  - Umansky, Viktor
AU  - Beckhove, Philipp
TI  - Tumor-specific regulatory T cells from the bone marrow orchestrate antitumor immunity in breast cancer.
JO  - Cancer immunology research
VL  - 7
IS  - 12
SN  - 2326-6074
CY  - Philadelphia, Pa.
PB  - AACR
M1  - DKFZ-2019-02523
SP  - 1998-2012
PY  - 2019
N1  - 7(12):1998-2012
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:31672785
DO  - DOI:10.1158/2326-6066.CIR-18-0763
UR  - https://inrepo02.dkfz.de/record/147406
ER  -