Núñez and Boari et al. characterized Treg in paired tumor-invaded (I) tumor-draining lymph node (TDLN), non-invaded (NI) TDLN, and primary luminal breast cancer tumors (T) and found that Treg frequency increased with nodal invasion. Tregs shared common transcriptional features and TCR clones between tumor and nodes, expressed higher levels of costimulatory and coinhibitory molecules (ICOS, GITR, OX40, CD39, PD-1, CTLA-4), and maintained their suppressive function in I TDNLs and tumors. In patients with breast cancer, high CD80:FOXP3 expression was associated with poor prognosis, and tumor Treg analysis suggests Treg CD80 as a therapeutic target.
Contributed by Shishir Pant
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.