Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients

Nicolas Gonzalo Núñez, Jimena Tosello Boari, Rodrigo Nalio Ramos, Wilfrid Richer, Nicolas Cagnard, Cyrill Dimitri Anderfuhren, Leticia Laura Niborski, Jeremy Bigot, Didier Meseure, Philippe Rochere, Maud Milder, Sophie Viel, Delphine Loirat, Louis Pérol, Anne Vincent-Salomon, Xavier Sastre-Garau, Becher Burkhard, Christine Sedlik, Olivier Lantz, Sebastian Amigorena and Eliane Piaggio ()
Additional contact information
Nicolas Gonzalo Núñez: PSL Research University, INSERM U932
Jimena Tosello Boari: PSL Research University, INSERM U932
Rodrigo Nalio Ramos: PSL Research University, INSERM U932
Wilfrid Richer: PSL Research University, INSERM U932
Nicolas Cagnard: Paris-Descartes Bioinformatics Platform
Cyrill Dimitri Anderfuhren: University of Zurich, Winterthurerstr. 190
Leticia Laura Niborski: PSL Research University, INSERM U932
Jeremy Bigot: PSL Research University, INSERM U932
Didier Meseure: PSL Research University, Departement de Biologie des Tumeurs
Philippe Rochere: PSL Research University, INSERM U932
Maud Milder: PSL Research University, Departement de Biologie des Tumeurs
Sophie Viel: PSL Research University, INSERM U932
Delphine Loirat: PSL Research University, INSERM U932
Louis Pérol: PSL Research University, INSERM U932
Anne Vincent-Salomon: PSL Research University, Departement de Biologie des Tumeurs
Xavier Sastre-Garau: PSL Research University, Departement de Biologie des Tumeurs
Becher Burkhard: University of Zurich, Winterthurerstr. 190
Christine Sedlik: PSL Research University, INSERM U932
Olivier Lantz: PSL Research University, INSERM U932
Sebastian Amigorena: PSL Research University, INSERM U932
Eliane Piaggio: PSL Research University, INSERM U932

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, and that Tregs express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17046-2

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DOI: 10.1038/s41467-020-17046-2

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