Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses
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Jacks_Regulatory t cells.pdf
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Author(s)
Bronson, Roderick T.
Joshi, Nikhil
Akama-Garren, Elliot H.
Lu, Yisi
Lee, Da-Yae
Chang, Gregory
Li, Amy
DuPage, Michel J.
Tammela, Tuomas
Kerper, Natanya R.
Date Issued
September 2015
Journal
Immunity
Publisher
Elsevier/Cell Press
Citation
Joshi, Nikhil S. et al. “Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-Tumor T Cell Responses.” Immunity 43.3 (2015): 579–590.
Version
Author's final manuscript
Abstract
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 lung adenocarcinoma model and
found Treg cells suppress anti-tumor responses in tumor-associated tertiary lymphoid structures (TA-TLS). TA-TLS have been described in human lung cancers, but their function remains to be determined. TLS 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-TLS upon Treg cell depletion, leading to tumor destruction. Thus, we propose Treg cells in TA-TLS can inhibit endogenous immune responses against tumors, and targeting these cells may provide therapeutic benefit for cancer patients.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.immuni.2015.08.006
