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

• Main Authors: Bronson, Roderick T (Author), Joshi, Nikhil (Contributor), Akama-Garren, Elliot H. (Contributor), Lu, Yisi (Contributor), Lee, Da-Yae (Contributor), Chang, Gregory (Contributor), Li, Amy (Contributor), DuPage, Michel J. (Contributor), Tammela, Tuomas (Contributor), Kerper, Natanya R. (Contributor), Farago, Anna F. (Contributor), Robbins, Rebecca (Contributor), Crowley, Denise G. (Contributor), Jacks, Tyler E. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: Elsevier/Cell Press, 2016-11-17T19:22:39Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051)
Howard Hughes Medical Institute
National Institutes of Health (U.S.) (Grants 1 U54 CA126515-01, R01-CA185020-01 and T32 GM007753)
Damon Runyon Cancer Research Foundation
John D. Proctor Foundation (Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award)
Lung Cancer Research Foundation
Howard Hughes Medical Institute (Investigator)
Daniel K. Ludwig Scholar