Anne Vincent-Salomon, Becher Burkhard, Delphine Loirat, Cyrill Dimitri Anderfuhren, Nicolas Cagnard, Jimena Tosello Boari, Wilfrid Richer, Christine Sedlik, Sophie Viel, Olivier Lantz, Louis Pérol, Xavier Sastre-Garau, Sebastian Amigorena, Nicolás Gonzalo Núñez, Didier Meseure, Rodrigo Nalio Ramos, Eliane Piaggio, Maud Milder, Philippe De La Rochere, Leticia Laura Niborski, Jeremy Bigot, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Zürich [Zürich] = University of Zurich (UZH), Bioinformatics Platform [Paris], Université Paris Descartes - Paris 5 (UPD5), Département de Biologie des Tumeurs, Institut Curie [Paris], Centre d'Investigation Clinique Biothérapie [Paris] (CICBT), Département d'Oncologie Médicale [Paris], Institut Curie [Paris]-Université Paris sciences et lettres (PSL), Department of Biopathology [Vandoeuvre-lès-Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, This work was funded by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Association pour la Recherche sur le Cancer (ARC), the Institut Curie, the Agence Nationale pour la Recherche (ANR Emergence program), the Institut National du Cancer (INCa), IGR-Curie 1428 Clinical Investigation Center, Labex DCBIOL (ANR-10-IDEX-0001-02 PSL and ANR-11-LABX0043), SIRIC (INCa-DGOS-Inserm_12554, projets 2011–2017:INCa-DGOS-Inserm_4654). N.G.N. received a fellowship from Ligue Nationale Contre le Cancer and the University Research Priority Program (URPP)., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Bodescot, Myriam, and Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID
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., Tumor-draining lymph nodes are often the first site of metastasis in breast cancer patients. Here, the authors show that metastatic lymph nodes are characterized by the accumulation of suppressive regulatory T cells with a distinct phenotype compared to matched non-invaded lymph nodes and tumors.