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

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 InstituteNational Institutes of Health (U.S.) (Grants 1 U54 CA126515-01, R01-CA185020-01 and T32 GM007753)Damon Runyon Cancer Research FoundationJohn D. Proctor Foundation (Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award)Lung Cancer Research FoundationHoward Hughes Medical Institute (Investigator)Daniel K. Ludwig Schola