Authors:	Muth, Sabine Klaric, Annekatrin Radsak, Markus Schild, Hansjörg Probst, Hans Christian
Title:	CD27 expression on Treg cells limits immune responses against tumors
Online publication date:	30-Aug-2022
Year of first publication:	2022
Language:	english
Abstract:	Regulatory T cells (Tregs) suppress immune responses and thus contribute to immune homeostasis. On the downside, Tregs also limit immune responses against tumors promoting the progression of cancer. Among the many mechanisms implied in Treg-mediated suppression, the inhibition of dendritic cells (DCs) has been shown to be central in peripheral tolerance induction as well as in cancers. We have shown previously that the maintenance of peripheral T cell tolerance critically depends on cognate interactions between Tregs and DCs and that the CTL priming by unsuppressed steady state DCs is mediated via CD70. Here, we have investigated whether the CD70/CD27 axis is also involved in Treg-mediated suppression of anti-tumor immunity. Using a mixed bone marrow chimeric mouse model in which we can deplete regulatory T cells in a temporally controlled fashion, we show that Treg-expressed CD27 prevents the breakdown of peripheral tolerance and limits anti-tumor immunity. Furthermore, ablation of Treg expressed CD27 acts synergistically with PD-1 checkpoint inhibition to improve CTL mediated immunity against a solid tumor. Our data thus identify Treg-expressed CD27 as a potential target in cancer immunotherapy. Key messages - Treg expressed CD27 maintains steady state DC tolerogenic - Treg expressed CD27 limits anti-tumor immunity - Ablation of Treg expressed CD27 synergizes with PD-1 blockade to improve CTL mediated tumor control
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7636
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Journal of molecular medicine 100
Pages or article number:	439 449
Publisher:	Springer
Publisher place:	Berlin u.a.
Issue date:	2022
ISSN:	1432-1440
Publisher DOI:	10.1007/s00109-021-02116-9
Appears in collections:	JGU-Publikationen