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

Núñez, Nicolas Gonzalo; Tosello Boari, Jimena; Ramos, Rodrigo Nalio; Richer, Wilfrid; Cagnard, Nicolas; Anderfuhren, Cyrill Dimitri; Niborski, Leticia Laura; Bigot, Jeremy; Meseure, Didier; De La Rochere, Philippe; Milder, Maud; Viel, Sophie; Loirat, Delphine; Pérol, Louis; Vincent-Salomon, Anne; Sastre-Garau, Xavier; Burkhard, Becher; Sedlik, Christine; Lantz, Olivier; Amigorena, Sebastian; Piaggio, Eliane

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.