Journal Article

DKFZ-2019-02523

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tumor-specific regulatory T cells from the bone marrow orchestrate antitumor immunity in breast cancer.

Ge, Y. (First author)DKFZ* ; Böhm, H.-H. (First author)DKFZ* ; Rathinasamy, A. (First author)DKFZ* ; Xydia, M.DKFZ* ; Hu, X.DKFZ* ; Pincha, M.DKFZ* ; Umansky, L.DKFZ* ; Breyer, C.DKFZ* ; Hillier, M.DKFZ* ; Bonertz, A.DKFZ* ; Sevko, A.DKFZ* ; Domschke, C. ; Schuetz, F. ; Frebel, H.DKFZ* ; Dettling, S. ; Herold-Mende, C. C. ; Reissfelder, C. ; Weitz, J. ; Umansky, V.DKFZ* ; Beckhove, P. (Last author)

2019
AACR Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/2326-6066.CIR-18-0763

Abstract: 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.

Note: 7(12):1998-2012

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Contributing Institute(s):

1. Translationale Immunologie (D015)
2. KKE Dermatoonkologie (A370)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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