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

Nat Commun. 2020 Jun 29;11(1):3272. doi: 10.1038/s41467-020-17046-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-1 Antigen / metabolism
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Immunosuppression Therapy
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis / immunology*
  • Lymphatic Metastasis / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • B7-1 Antigen