Abstract IA010: How opposing roles of interferon and pattern recognition receptor signaling in the TME influence immunotherapy

Abstract

Abstract Interferon (IFN) signaling pathways are broadly active across multiple cancer types. These pathways are typically associated with pathogen infection, but their roles in cancer are less understood. Emerging evidence indicates that IFN signaling has complex and even dichotomous roles in both cancer and host-pathogen interactions. On the one hand, IFN is often essential for immune activation and for promoting response to cancer immunotherapies. On the other hand, prolonged IFN signaling that accompanies persistent disease can lead to immunotherapy resistance and immunosuppression. This latter role represents a feedback inhibition mechanism that can also be observed in chronic pathogen infections to limit immune-mediated pathology. Thus, how these opposing effects of IFN signaling are controlled and what factors dictate one function over the other are important questions. In this presentation, insight into how opposing functions of IFN and pattern recognition receptor signaling impact cancer immunotherapy will be discussed. This will include evidence for what factors might favor one function of IFN over the other. Finally, work will be presented that illustrates how key interferon-stimulated genes (ISGs) expressed by cancer cells can control whether an immune stimulatory or suppressive tumor immune microenvironment develops. Citation Format: Andy J. Minn. How opposing roles of interferon and pattern recognition receptor signaling in the TME influence immunotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA010.