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

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Listed:
  • Nicolas Gonzalo Núñez

    (PSL Research University, INSERM U932
    University of Zurich, Winterthurerstr. 190)

  • 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
    Centre d’Investigation Clinique Biotherapie CICBT 1428, Institut Curie)

  • Philippe Rochere

    (PSL Research University, INSERM U932)

  • Maud Milder

    (PSL Research University, Departement de Biologie des Tumeurs
    Centre d’Investigation Clinique Biotherapie CICBT 1428, Institut Curie)

  • Sophie Viel

    (PSL Research University, INSERM U932)

  • Delphine Loirat

    (PSL Research University, INSERM U932
    Centre d’Investigation Clinique Biotherapie CICBT 1428, Institut Curie
    PSL Research University, Departement d’Oncologie Medicale)

  • Louis Pérol

    (PSL Research University, INSERM U932)

  • Anne Vincent-Salomon

    (PSL Research University, Departement de Biologie des Tumeurs
    Centre d’Investigation Clinique Biotherapie CICBT 1428, Institut Curie)

  • Xavier Sastre-Garau

    (PSL Research University, Departement de Biologie des Tumeurs
    6, avenue de Bourgogne CS 30519)

  • Becher Burkhard

    (University of Zurich, Winterthurerstr. 190)

  • Christine Sedlik

    (PSL Research University, INSERM U932
    Centre d’Investigation Clinique Biotherapie CICBT 1428, Institut Curie)

  • Olivier Lantz

    (PSL Research University, INSERM U932
    PSL Research University, Departement de Biologie des Tumeurs
    Centre d’Investigation Clinique Biotherapie CICBT 1428, Institut Curie)

  • Sebastian Amigorena

    (PSL Research University, INSERM U932
    Centre d’Investigation Clinique Biotherapie CICBT 1428, Institut Curie)

  • Eliane Piaggio

    (PSL Research University, INSERM U932
    Centre d’Investigation Clinique Biotherapie CICBT 1428, Institut Curie)

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.

Suggested Citation

  • Nicolas Gonzalo Núñez & Jimena Tosello Boari & Rodrigo Nalio Ramos & Wilfrid Richer & Nicolas Cagnard & Cyrill Dimitri Anderfuhren & Leticia Laura Niborski & Jeremy Bigot & Didier Meseure & Philippe R, 2020. "Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17046-2
    DOI: 10.1038/s41467-020-17046-2
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