Abstract A100: Downregulation of type 1 interferon receptor (IFNAR1) regulates the balance of regulatory T cells (Tregs) and cytotoxic T lymphocytes (CTLs) in tumor microenvironment

Abstract

Abstract Solid tumors are infiltrated by not only CD8+ effector T cells (CTLs) exerting tumoricidal function, but also by regulatory T cells (Tregs), which are a key barrier to antitumor immunity (1). In the tumor microenvironment, the type 1 interferon (IFN) signaling is downregulated due to proteolytic degradation of IFNAR1 (2). Reduced IFNAR1 levels in tumor stroma are important for establishing the immune privileged niche to support tumor development and progression (3). IFN pathway plays complex and controversial roles in regulating immune responses ([4-7). In this study, we show that loss of IFNAR1 leads to changes in the activities of Tregs and CTLs. Genetic stabilization of IFNAR1 (Ifnar1S526A, SA) recruits more CTLs in the tumor microenvironment; however, it does not change the frequency of Tregs. In addition, in SA tumor tissues, the CTLs appear to exhibit a greater tumoricidal activity. Furthermore, we find that SA Treg lost their inhibitory function and SA CTLs are resistant to Treg-mediated immune suppression. In all, we discuss putative mechanisms underlying these phenotypes that IFN pathway regulates the balance of Treg and CTL activities in the tumor microenvironment. Citation Format: Hongru Zhang, Jun Gui, Angelica Ortiz, Serge Fuchs. Downregulation of type 1 interferon receptor (IFNAR1) regulates the balance of regulatory T cells (Tregs) and cytotoxic T lymphocytes (CTLs) in tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A100.