Journal Article

DKFZ-2021-00397

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients.

Xydia, M. (First author)DKFZ* ; Rahbari, R. ; Ruggiero, E.DKFZ* ; Macaulay, I. ; Tarabichi, M. ; Lohmayer, R. ; Wilkening, S.DKFZ* ; Michels, T. ; Brown, D. ; Vanuytven, S. ; Mastitskaya, S. ; Laidlaw, S. ; Grabe, N. ; Pritsch, M.DKFZ* ; Fronza, R.DKFZ* ; Hexel, K.DKFZ* ; Schmitt, S.DKFZ* ; Müller-Steinhardt, M. ; Halama, N. ; Domschke, C. ; Schmidt, M.DKFZ* ; von Kalle, C.DKFZ* ; Schütz, F. ; Voet, T. ; Beckhove, P. (Last author)

2021
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-021-21297-y

Abstract: Regulatory 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.

Note: #EA:D015#LA:D015#

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Contributing Institute(s):

1. Translationale Immunologie (D015)
2. Zytometrie (W220)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2021

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