Abstract 4728: Iron regulation of innate immune pathogen-associated molecular pattern receptors

Abstract

Abstract Pathogen-associated molecular pattern (PAMP) receptors are key triggers of the pro-inflammatory immune effector functions of the cells of the innate immune system. Ectopic PAMP activation is a contributing factor to both cancer development and pathology, as well as host anti-tumor immune responses. Iron, an essential mineral in biological systems, has a similar dualistic role in cancer. We have shown that iron acts as a key modulator of intracellular signaling cascades downstream from PAMP activation. Cellular iron enrichment enhances the transcriptional activity of a pathogen-induced transcription factor downstream of PAMPs in an immortalized human macrophage cell line treated with a PAMP receptor-specific agonist ligand. Cell surface expression of the receptor was not affected by the iron enrichment; therefore, any modulation of receptor signaling by iron is likely downstream of the receptor. Furthermore, iron supplementation in vitro increases expression of immunity-related genes regulated by the pathogen-induced transcription factor; by contrast, treatment with iron-chelating reagents reduces expression of these genes. These results suggest that the iron content of the tumor microenvironment may have a regulatory role in pathological immunoregulation. In particular, the iron-retaining phenotype of many tumor cells may serve a novel pathological function, inhibiting PAMP-regulated anti-tumoral effector functions of tumor-infiltrating macrophages cells by iron deprivation. Citation Format: Evan Stater. Iron regulation of innate immune pathogen-associated molecular pattern receptors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4728.