Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses
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.; Farago, Anna F.; Robbins, Rebecca; Crowley, Denise G.; Jacks, Tyler E.; ... Show more Show less
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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology
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.
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