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

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Gonzalo Núñez, Nicolas | 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

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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