Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo

Research output: Contribution to journalArticlepeer-review

Authors

  • Attilio Bondanza
  • Valérie S Zimmermann
  • Patrizia Rovere-Querini
  • Javier Turnay
  • Christian M Stach
  • Reinhard E Voll
  • Udo S Gaipl
  • Wolf Bertling
  • Ernst Pöschl
  • Joachim R Kalden
  • Angelo A Manfredi
  • Martin Herrmann

Colleges, School and Institutes

Abstract

Strategies to enhance the immunogenicity of tumors are urgently needed. Although vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune response, its efficiency as immunogen is poor. Annexin V (AxV) binds with high affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and thereby impairs their uptake by macrophages. Here, we report that AxV preferentially targets irradiated lymphoma cells to CD8+ dendritic cells for in vivo clearance, elicits the release of proinflammatory cytokines and dramatically enhances the protection elicited against the tumor. The response was endowed with both memory, because protected animals rejected living lymphoma cells after 72 d, and specificity, because vaccinated animals failed to reject unrelated neoplasms. Finally, AxV-coupled irradiated cells induced the regression of growing tumors. These data indicate that endogenous adjuvants that bind to dying tumor cells can be exploited to target tumors for immune rejection.

Details

Original languageEnglish
Pages (from-to)1157-65
Number of pages9
JournalThe Journal of Experimental Medicine
Volume200
Issue number9
Publication statusPublished - 1 Nov 2004

Keywords

  • Animals, Annexin A5/immunology, Dendritic Cells/immunology, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Immunization, Lymphoma/immunology, Macrophages/immunology, Mice, Mice, Inbred C57BL, Phagocytosis/immunology, Receptors, Cell Surface/immunology, Tumor Cells, Cultured, Ultraviolet Rays

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