Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses

Immunity. 2015 Sep 15;43(3):579-90. doi: 10.1016/j.immuni.2015.08.006. Epub 2015 Sep 1.


Infiltration of regulatory T (Treg) cells into many tumor types correlates with poor patient prognoses. However, mechanisms of intratumoral Treg cell function remain to be elucidated. We investigated Treg cell function in a genetically engineered mouse model of lung adenocarcinoma and found that Treg cells suppressed anti-tumor responses in tumor-associated tertiary lymphoid structures (TA-TLSs). TA-TLSs have been described in human lung cancers, but their function remains to be determined. TLSs in this model were spatially associated with >90% of tumors and facilitated interactions between T cells and tumor-antigen-presenting dendritic cells (DCs). Costimulatory ligand expression by DCs and T cell proliferation rates increased in TA-TLSs upon Treg cell depletion, leading to tumor destruction. Thus, we propose that Treg cells in TA-TLSs can inhibit endogenous immune responses against tumors, and targeting these cells might provide therapeutic benefit for cancer patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Immunohistochemistry
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocyte Depletion
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Luminescent Proteins