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000167532 1001_ $$0P:(DE-He78)d3f0a48c15b355dfeae29fd5137d8bcb$$aXydia, Maria$$b0$$eFirst author
000167532 245__ $$aCommon clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients.
000167532 260__ $$a[London]$$bNature Publishing Group UK$$c2021
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000167532 520__ $$aRegulatory CD4+ T cells (Treg) prevent tumor clearance by conventional T cells (Tconv) comprising a major obstacle of cancer immune-surveillance. Hitherto, the mechanisms of Treg repertoire formation in human cancers remain largely unclear. Here, we analyze Treg clonal origin in breast cancer patients using T-Cell Receptor and single-cell transcriptome sequencing. While Treg in peripheral blood and breast tumors are clonally distinct, Tconv clones, including tumor-antigen reactive effectors (Teff), are detected in both compartments. Tumor-infiltrating CD4+ cells accumulate into distinct transcriptome clusters, including early activated Tconv, uncommitted Teff, Th1 Teff, suppressive Treg and pro-tumorigenic Treg. Trajectory analysis suggests early activated Tconv differentiation either into Th1 Teff or into suppressive and pro-tumorigenic Treg. Importantly, Tconv, activated Tconv and Treg share highly-expanded clones contributing up to 65% of intratumoral Treg. Here we show that Treg in human breast cancer may considerably stem from antigen-experienced Tconv converting into secondary induced Treg through intratumoral activation.
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000167532 7001_ $$00000-0002-1839-7785$$aRahbari, Raheleh$$b1
000167532 7001_ $$0P:(DE-He78)606957afb35b517e3fdd526379767c48$$aRuggiero, Eliana$$b2
000167532 7001_ $$aMacaulay, Iain$$b3
000167532 7001_ $$aTarabichi, Maxime$$b4
000167532 7001_ $$aLohmayer, Robert$$b5
000167532 7001_ $$0P:(DE-He78)928f784868a4b5ff301367ecda92f152$$aWilkening, Stefan$$b6
000167532 7001_ $$aMichels, Tillmann$$b7
000167532 7001_ $$aBrown, Daniel$$b8
000167532 7001_ $$aVanuytven, Sebastiaan$$b9
000167532 7001_ $$00000-0002-4819-2908$$aMastitskaya, Svetlana$$b10
000167532 7001_ $$00000-0001-7658-1428$$aLaidlaw, Sean$$b11
000167532 7001_ $$aGrabe, Niels$$b12
000167532 7001_ $$0P:(DE-HGF)0$$aPritsch, Maria$$b13
000167532 7001_ $$0P:(DE-He78)c2585457f370249465a2080111937cf5$$aFronza, Raffaele$$b14
000167532 7001_ $$0P:(DE-He78)8e8f777853496a781f0c651d77c36abf$$aHexel, Klaus$$b15$$udkfz
000167532 7001_ $$0P:(DE-He78)9743d171a21db4cf055df4dcf0153153$$aSchmitt, Steffen$$b16$$udkfz
000167532 7001_ $$aMüller-Steinhardt, Michael$$b17
000167532 7001_ $$aHalama, Niels$$b18
000167532 7001_ $$aDomschke, Christoph$$b19
000167532 7001_ $$0P:(DE-He78)b91bec47a4148ba68a58ab292d5860f2$$aSchmidt, Manfred$$b20$$udkfz
000167532 7001_ $$0P:(DE-He78)5bacb661d5d7c0220d8f996d980ad8de$$avon Kalle, Christof$$b21$$udkfz
000167532 7001_ $$aSchütz, Florian$$b22
000167532 7001_ $$aVoet, Thierry$$b23
000167532 7001_ $$0P:(DE-He78)1732377f6242a18280bc6aaa196988d1$$aBeckhove, Philipp$$b24$$eLast author
000167532 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-021-21297-y$$gVol. 12, no. 1, p. 1119$$n1$$p1119$$tNature Communications$$v12$$x2041-1723$$y2021
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