Exosome-Containing Preparations From Postirradiated Mouse Melanoma Cells Delay Melanoma Growth In Vivo by a Natural Killer Cell-Dependent Mechanism

• Type of Material: Article
• Authors: Kishore Kumar Jella, Emory University; Tahseen H. Nasti, Emory University; Zhentian Li, Emory University; David Lawson, Emory University; Jeffrey Switchenko, Emory University; Rafi Ahmed, Emory University; William Dynan, Emory University; Mohammad Khan, Emory University
• Language: English
• Date: 2020-09-01
• Publisher: ELSEVIER SCIENCE INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2020
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ijrobp.2020.06.016
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
• Volume: 108
• Issue: 1
• Start Page: 104
• End Page: 114
• Grant/Funding Information: This work was supported by Winship Invest$ Pilot Grants to M.K.K. and W.S.D. Additional support was received from an American Cancer Society Institutional Research Grant (ACS#126815-IRG-14-188-01-IRG to M.K.K.), a Department of Radiation Oncology Pilot Grant, a Melanoma Seed Grant from the Melanoma Team at the Winship Cancer Institute, and awards from the US National Aeronautics and Space Administration to W.S.D. (NNX15AD63G and 80NSSC18K1116).
• Keywords: HEAT-SHOCK PROTEINS; CANCER-CELLS; DNA; MICROENVIRONMENT; RADIATION; RELEASE; BIOLOGY; Science & Technology; Radiology, Nuclear Medicine & Medical Imaging; Life Sciences & Biomedicine; INNATE; SECRETION; PATHWAY; Oncology
• Research Categories: Biology, Genetics; Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

Purpose: To investigate the ability of radiation to stimulate exosome release from melanoma cells and to characterize the resulting exosome-containing vesicle preparations for their ability to promote a host antitumor immune response. Materials and Methods: Cultured B16F10 murine melanoma cells or tumors were irradiated, and secreted extracellular vesicles were isolated and characterized. The exosome-containing vesicle preparations were injected into fresh tumors in syngeneic mice, and tumor growth and infiltrating T cells and natural killer (NK) cells were characterized. Results: Irradiation stimulated exosome release from B16F10 murine melanoma cells. Exosome preparations from irradiated cell culture supernatants were biologically active, as demonstrated by uptake into recipient cells and by the ability to induce dendritic cell maturation and activation in vitro. Intratumoral injection significantly delayed tumor growth in vivo, whereas injection of similar preparations from non irradiated cells had no effect. The antitumor effect was correlated to an increase in interferon gamma–producing tumor-infiltrating NK cells. Pretreatment of the host mice with anti-NK cell antibodies abolished the effect, whereas pretreatment with anti-CD8+ T-cell antibodies did not. Conclusion: Exosomes from irradiated cells, or synthetic mimics, might provide an effective strategy for potentiation of NK cell–mediated host antitumor immunity.