This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shaif-Muthana, M. Articles by Murray, A. Search for Related Content PubMed PubMed Citation Articles by Shaif-Muthana, M. Articles by Murray, A.

Dead or Alive: Immunogenicity of Human Melanoma Cells When Presented by Dendritic Cells¹

Institute for Cancer Studies, Division of Oncology and Cellular Pathology, University of Sheffield Medical School, Sheffield, S10 2RX [M. S-M., C. M., A. M.], and Department of Ophthalmology and Orthoptics, Royal Hallamshire Hospital, Sheffield, S10 2JF [K. S., I. R.], United Kingdom

Uveal melanoma is an aggressive malignancy with a poor prognosis despite current therapeutic intervention. These tumors have been shown to be antigenic because they express a number of melanoma-associated antigens and are therefore attractive targets for immunotherapy. Here, we investigated the immunogenicity of uveal melanoma cells that have undergone apoptosis and compared this with their necrotic or live counterparts. The fate of the tumor antigens in these cells largely depends on their ability to be processed and phagocytosed by dendritic cells (DCs). Flow cytometric analysis shows that human DCs form conjugates more efficiently with dead uveal melanoma cells, and consequently these are effective stimuli of lymphocyte proliferation. However, only DCs pulsed with apoptotic cells were able to induce proliferation of CD8⁺ cytotoxic T cells and stimulate antigen-specific T cells. This study demonstrates for the first time that DCs derived from melanoma patients process and present antigens derived from both HLA-matched or HLA-mismatched human apoptotic tumor cells stimulating both CD4⁺ and CD8⁺ T cells. This approach may be important to the development of DC-based immunotherapies for melanoma.

This article has been cited by other articles:

				Y.-s. Wang, D. Li, H.-s. Shi, Y.-j. Wen, L. Yang, N. Xu, X.-c. Chen, X. Chen, P. Chen, J. Li, et al. Intratumoral Expression of Mature Human Neutrophil Peptide-1 Mediates Antitumor Immunity in Mice Clin. Cancer Res., November 15, 2009; 15(22): 6901 - 6911. [Abstract] [Full Text] [PDF]

				M. R. Shurin, A. I. Potapovich, Y. Y. Tyurina, I. L. Tourkova, G. V. Shurin, and V. E. Kagan Recognition of Live Phosphatidylserine-Labeled Tumor Cells by Dendritic Cells: A Novel Approach to Immunotherapy of Skin Cancer Cancer Res., March 15, 2009; 69(6): 2487 - 2496. [Abstract] [Full Text] [PDF]

				M. E Polak, N. J Borthwick, P. Johnson, J. L Hungerford, B. Higgins, S. Di Palma, M. J Jager, and I. A Cree Presence and phenotype of dendritic cells in uveal melanoma Br J Ophthalmol, July 1, 2007; 91(7): 971 - 976. [Abstract] [Full Text] [PDF]

				D. H. Schuurhuis, N. van Montfoort, A. Ioan-Facsinay, R. Jiawan, M. Camps, J. Nouta, C. J. M. Melief, J. S. Verbeek, and F. Ossendorp Immune complex-loaded dendritic cells are superior to soluble immune complexes as antitumor vaccine. J. Immunol., April 15, 2006; 176(8): 4573 - 4580. [Abstract] [Full Text] [PDF]

				P. R. Hoffmann, J. A. Kench, A. Vondracek, E. Kruk, D. L. Daleke, M. Jordan, P. Marrack, P. M. Henson, and V. A. Fadok Interaction between Phosphatidylserine and the Phosphatidylserine Receptor Inhibits Immune Responses In Vivo J. Immunol., February 1, 2005; 174(3): 1393 - 1404. [Abstract] [Full Text] [PDF]

				V. S. Zimmermann, A. Bondanza, A. Monno, P. Rovere-Querini, A. Corti, and A. A. Manfredi TNF-{alpha} Coupled to Membrane of Apoptotic Cells Favors the Cross-Priming to Melanoma Antigens J. Immunol., February 15, 2004; 172(4): 2643 - 2650. [Abstract] [Full Text] [PDF]

				R. S. Goldszmid, J. Idoyaga, A. I. Bravo, R. Steinman, J. Mordoh, and R. Wainstok Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma J. Immunol., December 1, 2003; 171(11): 5940 - 5947. [Abstract] [Full Text] [PDF]

				M. R. Muller, F. Grunebach, A. Nencioni, and P. Brossart Transfection of Dendritic Cells with RNA Induces CD4- and CD8-Mediated T Cell Immunity Against Breast Carcinomas and Reveals the Immunodominance of Presented T Cell Epitopes J. Immunol., June 15, 2003; 170(12): 5892 - 5896. [Abstract] [Full Text] [PDF]

				A. K. Nowak, R. A. Lake, A. L. Marzo, B. Scott, W. R. Heath, E. J. Collins, J. A. Frelinger, and B. W. S. Robinson Induction of Tumor Cell Apoptosis In Vivo Increases Tumor Antigen Cross-Presentation, Cross-Priming Rather than Cross-Tolerizing Host Tumor-Specific CD8 T Cells J. Immunol., May 15, 2003; 170(10): 4905 - 4913. [Abstract] [Full Text] [PDF]

				K. Akiyama, S. Ebihara, A. Yada, K. Matsumura, S. Aiba, T. Nukiwa, and T. Takai Targeting Apoptotic Tumor Cells to Fc{gamma}R Provides Efficient and Versatile Vaccination Against Tumors by Dendritic Cells J. Immunol., February 15, 2003; 170(4): 1641 - 1648. [Abstract] [Full Text] [PDF]

				A. Bondanza, V. S. Zimmermann, G. Dell'Antonio, E. Dal Cin, A. Capobianco, M. G. Sabbadini, A. A. Manfredi, and P. Rovere-Querini Cutting Edge: Dissociation Between Autoimmune Response and Clinical Disease After Vaccination with Dendritic Cells J. Immunol., January 1, 2003; 170(1): 24 - 27. [Abstract] [Full Text] [PDF]

				M. Schnurr, C. Scholz, S. Rothenfusser, P. Galambos, M. Dauer, J. Robe, S. Endres, and A. Eigler Apoptotic Pancreatic Tumor Cells Are Superior to Cell Lysates in Promoting Cross-Priming of Cytotoxic T Cells and Activate NK and {gamma}{delta} T Cells Cancer Res., April 1, 2002; 62(8): 2347 - 2352. [Abstract] [Full Text] [PDF]

				G. Pietra, R. Mortarini, G. Parmiani, and A. Anichini Phases of Apoptosis of Melanoma Cells, but not of Normal Melanocytes, Differently Affect Maturation of Myeloid Dendritic Cells Cancer Res., November 1, 2001; 61(22): 8218 - 8226. [Abstract] [Full Text] [PDF]