Radiation and Cancer Biology

SS 43 - Biology 8 - Radiation and the Immune Response Session II

319 - Post-Irradiated Tumor-Derived Exosomes Lead to Melanoma Tumor Growth Delay, Potentially Mediated by Death Associated Molecular Pattern (DAMPs) Proteins

Wednesday, October 24
4:05 PM - 4:15 PM
Location: Room 004

Post-Irradiated Tumor-Derived Exosomes Lead to Melanoma Tumor Growth Delay, Potentially Mediated by Death Associated Molecular Pattern (DAMPs) Proteins
K. K. Jella1, T. Nasti2, Z. Li3, D. Lawson4, R. Ahmed2, W. S. Dynan3, and M. K. Khan5; 1Emory University Winship Cancer Institute, Atlanta, GA, 2Department of Microbiology/Immunology, Emory University, Atlanta, GA, 3Winship Cancer Institute, Atlanta, GA, 4Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, 5Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA

Purpose/Objective(s): Exosomes mediate communication between irradiated and bystander cells in vitro. Exosomes have also been shown to mediate tumor-host communication in a variety of settings in vivo. Here we investigate the properties of exosomes from irradiated melanoma cells and tumors and test their ability to transfer radiation effects to fresh, non-irradiated tumors.

Materials/Methods: Experiments were performed using the mouse B16F10 melanoma model. Tumor cells were irradiated at single fraction doses up to 20 Gy, exosomes were isolated from conditioned medium, and physical, biochemical, and biological properties were investigated. Additionally, an in vivo model for local abscopal effects was established based on bilateral engraftment of tumor cells in syngeneic mice. Exosomes were prepared from irradiated cells or tumors, injected into fresh tumors in a different mouse, and tumor growth was monitored at the ipsilateral and contralateral sites.

Results: Irradiation stimulated exosome release from B16F10GP melanoma cells by up to 5-fold. Exosomes from irradiated cells were associated with damage associated molecular patterns including calreticulin, HSP70, and high mobility group B1 protein and with other stress-related proteins. Exosomes from irradiated cells were preferentially taken up by both melanoma cells and primary dendritic cells, and this uptake led to dendritic cell activation. Intratumoral injection of exosomes derived after irradiation brought about growth delay at the ipsilateral, but not contralateral site.

Conclusion: Radiation stimulates exosome release from B16F10GP cells, as a function of radiation dose. Exosomes derived from irradiated cells or tumors can transfer anti-tumor effects of radiotherapy to radiation-naïve B16F10GP melanomas. We suggest that exosomes containing radiation induced damage associated molecular patterns may be activating dendritic cells, and hence, leading to exosome mediated tumor control.

Author Disclosure: K. Jella: None. Z. Li: None. D. Lawson: None.

Kishore Kumar Jella, PhD

Disclosure:
No relationships to disclose.

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Send Email for Kishore Kumar Jella


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