Recognition of Live Phosphatidylserine-Labeled Tumor Cells by Dendritic Cells: A Novel Approach to Immunotherapy of Skin Cancer

Departments of ¹Pathology and ²Immunology, University of Pittsburgh Medical Center, ³Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania

^* To whom correspondence should be addressed. E-mail: kagan{at}pitt.edu.

	Abstract

Dendritic cells (DC) loaded with tumor antigens from apoptotic/necrotic tumor cells are commonly used as vaccines for cancer therapy. However, the use of dead tumor cells may cause both tolerance and immunity, making the effect of vaccination unpredictable. To deliver live tumor "cargoes" into DC, we developed a new approach based on the "labeling" of tumors with a phospholipid "eat-me" signal, phosphatidylserine. Expression of phosphatidylserine on live tumor cells mediated their recognition and endocytosis by DC resulting in the presentation of tumor antigens to antigen-specific T cells. In mice, topical application of phosphatidylserine-containing ointment over melanoma induced tumor-specific CTL, local and systemic antitumor immunity, and inhibited tumor growth. Thus, labeling of tumors with phosphatidylserine is a promising strategy for cancer immunotherapy. [Cancer Res 2009;69(6):2487–96]

Key Words: Phosphatidylserine, Dendritic cells, Melanoma, Lymphoma, Topical therapy, Apoptosis, Necrosis, Endocytosis

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