Abstract 127: Exosomes derived from head and neck cancer enhance the cytotoxicities of NK cells by NAP1-IRF-3 pathway

Abstract

Abstract Objective: To examine the effect of tumor-derived exosomes (TEXs) from oral cancer on natural killer (NK) cells and to explore the underlying mechanism. Materials and Methods: TEXs were isolated from the medium supernatant of oral cancer (OC) cells using ultrafiltration and affinity chromatography and were identified using electronic microscopy, nanoparticle tracking analysis and immunoblotting. The effects of TEXs on NK cells were analyzed using laser scanning confocal microscopy and several functional assays of NK cells. To explore the mechanism, antibody array, protein mass spectrometry and RNA interference were adopted. Results: The particles isolated from the OC cells were identified as exosomes with satisfactory morphology, concentration and purity. The TEXs were internalized by the NK cells and then promoted the biologic functions of these cells, including proliferation, cytotoxicity and the release of perforin and granzyme M. Furthermore, we found that the TEXs increased the expression of interferon regulatory factor 3 (IRF-3) and phosphorylated IRF-3 by antibody array, which drove the expression of the type I interferon (IFN) gene and the chemokine (C-X-C motif) ligand (CXCL) genes, thereby promoting the function of NK cells. We also found that NF-κB-activating kinase-associated protein 1 (NAP1), an upstream activator of IRF-3, was enriched in TEXs, and treatment with TEXs increased NAP1 in NK cells. Importantly, NAP1-depleted TEXs obtained from OC cells dramatically weakened the influence of the TEXs on NK cells. Conclusion: Our findings reveal a previously unrecognized function of exosome derived from oral cancer cells in enhancing the cytotoxicity of NK cells by NAP1- IRF-3 pathway. This work was supported by the National Program on Key Research Project of China (2016YFC0902700). Citation Format: Wantao Chen, Yingnan Wang, Jianjun Zhang. Exosomes derived from head and neck cancer enhance the cytotoxicities of NK cells by NAP1-IRF-3 pathway [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 127.