1. ¹INSERM, Unité 638, Nice, France
2. ²Faculté de Médecine, Université de Nice Sophia Antipolis, Nice, France
3. ³Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
4. ⁴Service de Chirurgie Générale et Digestive, Centre Hospitalier Princesse Grace, Monaco
5. ⁵Service de Chirurgie d'Urgence, Hôpital St Roch, Nice, France
6. ⁶Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
7. ⁷Department of Biochemistry, University of Coimbra, Coimbra, Portugal

Correspondence: Dr V Pierrefite-Carle, INSERM, Unité 638, Faculté de Médecine, Université de Nice Sophia Antipolis, Avenue de Valombrose, 06107 Nice cédex 2, France. E-mail: pierrefi@unice.fr

⁸These authors contributed equally to this work.

Received 11 March 2007; Revised 26 April 2007; Accepted 26 May 2007; Published online 22 June 2007.

Abstract

The bacterial cytosine deaminase (CD) gene converts the non-toxic prodrug 5-fluorocytosine (5-FC) into 5-fluorouracil. We have previously shown, in a rat liver metastasis model from colon carcinoma, that intratumoral injection of a CD-expressing plasmid into the animals followed by 5-FC treatment results in the regression of the treated tumor as well as distant uninjected tumors. The aim of this study was to further analyze the mechanisms associated with tumor regression induced upon application of suicide CD/5-FC strategy. Tumor regression was associated with an increased apoptosis, the recruitment of natural killer cells, CD4- and CD8 T lymphocytes within the tumors and an increased expression of several cytokines/chemokines mRNAs. These data indicate that the CD/5-FC suicide strategy is associated with the triggering of cellular and molecular events leading to an efficient antitumor immune response involving both innate and acquired immunity.