HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print June 20, 2008

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0108075v1 84/3/713    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Buonocore, S. Articles by Flamand, V. PubMed PubMed Citation Articles by Buonocore, S. Articles by Flamand, V.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0108075

Received for publication January 31, 2008.
Revised May 26, 2008.
Accepted for publication May 26, 2008.

Article

Neutrophil-dependent tumor rejection and priming of tumoricidal CD8⁺ T cell response induced by dendritic cells overexpressing CD95L

Sofia Buonocore ^*, Najate Ouled Haddou ^*, Fabrice Moore ^*, Sandrine Florquin , Frédéric Paulart ^*, Carlo Heirman , Kris Thielemans , Michel Goldman ^*, and Véronique Flamand ^*@

*Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium; Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of Vrije Universiteit Brussel, Brussels, Belgium

^@ To whom correspondence should be addressed. E-mail: vflamand{at}ulb.ac.be.

	Abstract

Overexpression of CD95 (Fas/Apo-1) ligand (CD95L) has been shown to induce T cell tolerance but also, neutrophilic inflammation and rejection of allogeneic tissue. We explored the capacity of dendritic cells (DCs) genetically engineered to overexpress CD95L to induce an antitumor response. We first found that DCs overexpressing CD95L, in addition to MHC class I-restricted OVA peptides (CD95L-OVA-DCs), induced increased antigen-specific CD8⁺ T cell responses as compared with DCs overexpressing OVA peptides alone. The enhanced T cell responses were associated with improved regression of a tumor expressing OVA, allowing survival of all animals. When DCs overexpressing CD95L (CD95L-DCs) were injected with the tumor expressing OVA, in vivo tumor proliferation was strikingly inhibited. A strong cellular apoptosis and a massive neutrophilic infiltrate developed in this setting. Neutrophil depletion prevented tumor regression as well as enhanced IFN- production induced by CD95L-OVA-DCs. Furthermore, the CD8⁺ T cell response induced by the coadministration of tumor cells and CD95L-DCs led to rejection of a tumor implanted at a distance from the DC injection site. In summary, DCs expressing CD95L promote tumor rejection involving neutrophil-mediated innate immunity and CD8⁺ T cell-dependent adaptative immune responses.

Key Words: murine model • immunotherapy • CD95 ligand