Regulatory T-cells (Treg) are a T-cell lineage vital to promoting tolerance to self antigens, commensal bacteria, and environmental antigens, as well as limiting responses to acute and chronic infections. Because of their critical role in immunosuppression in diverse biologic settings—including the tumor microenvironment—therapeutic targeting of Treg cells holds promise for cancer immunotherapy. In addition to dampening immune responses against tumor antigens and the associated inflammation, tissue-resident Treg cells may directly support tumor growth, homeostasis, and metastasis. Hence, understanding Treg cell functions independent from immunomodulation may provide novel targets for cancer therapy without the adverse side effects associated with immune checkpoint blockade. Studies of Treg cells found in non-lymphoid tissues have revealed transcriptional signatures and functions distinguishable from those found in Treg cells residing in secondary lymphoid organs, suggesting that Treg cells may perform a variety of specialized functions within non-lymphoid tissues. In addition, Treg cells can show distinct localization within non-lymphoid organs, raising the possibility that they may interact with different immune and non-immune tissue resident cells. In particular, we find frequent Treg cell localization in close proximity to peripheral neurons. Gene expression analysis has revealed expression of neuromodulatory molecules by Treg cells, further suggesting interplay between Treg cells and peripheral neurons. Interactions between Treg cells and the peripheral nervous system may play an important role in limiting immune responses and/or promoting tissue homeostasis. Understanding potential neuromodulatory activity of Treg cells and its effect on inflammation, tissue homeostasis and cancer could reveal novel strategies for therapeutic possibilities.

Citation Format: Alejandra Mendoza. Role of nonimmune functions of regulatory T-cells in inflammation and tissue homeostasis [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A203.