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Efficient Cross-presentation Depends on Autophagy in Tumor Cells

¹ Laboratory of Cancer Immunobiology, ² Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, and ³ Department of Radiation Oncology, Oregon Health and Science University, Portland, Oregon

Requests for reprints: Hong-Ming Hu, Providence Portland Medical Center, 4805 Northeast Glisan Street, Portland, OR 97213-2967. Phone: 503-215-6531; Fax: 503-215-6841; E-mail: hhu{at}providence.org.

Key Words: Autophagy • Antigen cross-presentation • DC • Autophagosome

Cross-presentation of antigens is critical for the induction of adaptive immunity against tumor cells and infectious pathogens. Currently, it is not known how cross-presentation of tumor antigens is regulated by autophagy. Using both HEK 293T cells that expressed the model antigen OVA and melanoma cells as antigen donors, we show that macroautophagy in tumor cells is essential for cross-presentation by dendritic cells both in vitro and in vivo. Inhibition of autophagy abolished cross-presentation almost completely, whereas induction of autophagy dramatically enhanced the cross-presentation of tumor antigens. Moreover, purified autophagosomes were found to be efficient antigen carriers for cross-presentation. Our findings not only identified a novel role for autophagy as an active process in antigen sequestration and delivery to dendritic cells for cross-presentation, but also suggested, for the first time, that isolated autophagosomes may have potential as potent vaccines for immunotherapy against cancer and infectious diseases. [Cancer Res 2008;68(17):6889–95]

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