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000147406 0247_ $$2doi$$a10.1158/2326-6066.CIR-18-0763
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000147406 1001_ $$0P:(DE-He78)a680dbb93cb7ae62c0456b04cb13567b$$aGe, Yingzi$$b0$$eFirst author
000147406 245__ $$aTumor-specific regulatory T cells from the bone marrow orchestrate antitumor immunity in breast cancer.
000147406 260__ $$aPhiladelphia, Pa.$$bAACR$$c2019
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000147406 520__ $$aEndogenous antitumor effector T cell responses and immune suppressive regulatory T cells (Tregs) critically influence the prognosis of cancer patients, yet many of the mechanisms of how this occurs remain unresolved. Based on an analysis of the function, antigen-specificity and distribution of tumor antigen-reactive T cells and Tregs in breast cancer patients and transgenic mouse tumor models we showed that tumor-specific Tregs were selectively activated in the bone marrow (BM) and egressed into the peripheral blood (PB). The BM was constantly depleted of tumor-specific Tregs and was instead a site of increased induction and activity of tumor-reactive effector/memory T cells. Treg egress from the BM was associated with activation-induced expression of peripheral homing receptors such as CCR2. Since breast cancer tissues express the CCR2 ligand CCL2, the activation and egress of tumor antigen-specific Tregs in the BM resulted in the accumulation of Tregs in breast tumor tissue. Such immune-compartmentalization and redistribution of T cell subpopulations between the BM and peripheral tissues was achieved by vaccination with adenoviral vector encoded TRP-2 tumor antigen in a RET transgenic mouse model of spontaneous malignant melanoma. Thus, the BM simultaneously represented a source of tumor-infiltrating Tregs and a site for the induction of endogenous tumor-specific effector T cell responses, suggesting that both antitumor immunity and local immune suppression are orchestrated in the BM.
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000147406 7001_ $$0P:(DE-He78)bdea8d359afbb726cce05b82d7b01669$$aBöhm, Hans-Henning$$b1$$eFirst author
000147406 7001_ $$0P:(DE-He78)a4d37cf08789986f17ff6ceb579e396e$$aRathinasamy, Anchana$$b2$$eFirst author
000147406 7001_ $$0P:(DE-He78)d3f0a48c15b355dfeae29fd5137d8bcb$$aXydia, Maria$$b3
000147406 7001_ $$0P:(DE-He78)9f73dd6f3a8b9ba22a653f5d0257bd6f$$aHu, Xiaoying$$b4
000147406 7001_ $$0P:(DE-He78)74f34d9a816946005cede7ae8df5b260$$aPincha, Mudita$$b5
000147406 7001_ $$0P:(DE-He78)d5882ffec9d5dea0104c7d33165e4a45$$aUmansky, Ludmila$$b6
000147406 7001_ $$0P:(DE-HGF)0$$aBreyer, Christopher$$b7
000147406 7001_ $$0P:(DE-HGF)0$$aHillier, Michael$$b8
000147406 7001_ $$00000-0002-6846-9265$$aBonertz, Andreas$$b9
000147406 7001_ $$0P:(DE-HGF)0$$aSevko, Alexandra$$b10
000147406 7001_ $$aDomschke, Christoph$$b11
000147406 7001_ $$aSchuetz, Florian$$b12
000147406 7001_ $$0P:(DE-HGF)0$$aFrebel, Helge$$b13
000147406 7001_ $$aDettling, Steffen$$b14
000147406 7001_ $$aHerold-Mende, Christel C$$b15
000147406 7001_ $$aReissfelder, Christoph$$b16
000147406 7001_ $$aWeitz, Juergen$$b17
000147406 7001_ $$0P:(DE-He78)38be34240daf8b47325afc7910e77f7b$$aUmansky, Viktor$$b18
000147406 7001_ $$0P:(DE-He78)1732377f6242a18280bc6aaa196988d1$$aBeckhove, Philipp$$b19$$eLast author
000147406 773__ $$0PERI:(DE-600)2732517-9$$a10.1158/2326-6066.CIR-18-0763$$gp. canimm.0763.2018 -$$n12$$p1998-2012$$tCancer immunology research$$v7$$x2326-6074$$y2019
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