TY - JOUR
T1 - Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients
AU - Xydia, Maria
AU - Rahbari, Raheleh
AU - Ruggiero, Eliana
AU - Macaulay, Iain
AU - Tarabichi, Maxime
AU - Lohmayer, Robert
AU - Wilkening, Stefan
AU - Michels, Tillmann
AU - Brown, Daniel
AU - Vanuytven, Sebastiaan
AU - Mastitskaya, Svetlana
AU - Laidlaw, Sean
AU - Grabe, Niels
AU - Pritsch, Maria
AU - Fronza, Raffaele
AU - Hexel, Klaus
AU - Schmitt, Steffen
AU - Müller-Steinhardt, Michael
AU - Halama, Niels
AU - Domschke, Christoph
AU - Schmidt, Manfred
AU - von Kalle, Christof
AU - Schütz, Florian
AU - Voet, Thierry
AU - Beckhove, Philipp
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85101218252
U2 - 10.1038/s41467-021-21297-y
DO - 10.1038/s41467-021-21297-y
M3 - Article
C2 - 33602930
AN - SCOPUS:85101218252
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1119
ER -