Abstract 2012: UVB-induced ULBP1 upregulation in melanocytes depends on HMGB1-mediated activation of NF-κB and IRF3

Abstract

Abstract Anti-tumor immune surveillance mediated by innate immunity cells such as NK cells plays a critical role in eliminating “damaged” cells at precancerous stage and preventing cancer progression. As a key epidemiological factor associated with melanoma, solar UV radiation also elicit immunosurveillance by upregulating ligands for NK cell activating receptor NKG2D. Nevertheless, how UVR upregulates NKG2DL in melanocytes is not completely understood. We found UVB exposure induced secretion of damage-associated molecular patterns molecule HMGB1 from skin cells. HMGB1 activates transcription factors NF-κB and IRF3 in melanocytes which synergistically enhances NKG2D ligand ULBP1 transcription. Moreover, RAGE is essential for HMGB1-induced activation of NF-κB and IRF3, which serves as the HMGB1 receptor and mediates activation of TBK1. Consistently, HMGB1 deficient melanoma cells are less susceptible to NK cells mediated cytotoxicity. Our study provides a mechanistic link between environmental UV radiation and antitumor immunosurveillance induced in melanocytes, which may play a critical role in the early stages of melanomagenesis. Citation Format: Zhaohui Wu, Wei Wang. UVB-induced ULBP1 upregulation in melanocytes depends on HMGB1-mediated activation of NF-κB and IRF3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2012. doi:10.1158/1538-7445.AM2017-2012