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Cancer Research 69, 2487, March 15, 2009. Published Online First March 10, 2009;
doi: 10.1158/0008-5472.CAN-08-2611
© 2009 American Association for Cancer Research

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Immunology

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

Michael R. Shurin1,2, Alla I. Potapovich3, Yulia Y. Tyurina3, Irina L. Tourkova1, Galina V. Shurin1 and Valerian E. Kagan3

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

Requests for reprints: Valerian E. Kagan, Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA. Phone: 412-624-9479; Fax: 412-624-9361; E-mail: kagan{at}pitt.edu or Michael R. Shurin, Clinical Immunopathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA; Phone: 412-647-6140; Fax: 412-648-8158; E-mail: shurinmr{at}upmc.edu.

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

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]




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G. V. Shurin, I. L. Tourkova, R. Kaneno, and M. R. Shurin
Chemotherapeutic Agents in Noncytotoxic Concentrations Increase Antigen Presentation by Dendritic Cells via an IL-12-Dependent Mechanism
J. Immunol., July 1, 2009; 183(1): 137 - 144.
[Abstract] [Full Text] [PDF]




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Copyright © 2009 by the American Association for Cancer Research.