Email updates

Keep up to date with the latest news and content from Retrovirology and BioMed Central.

This article is part of the supplement: 2005 International Meeting of The Institute of Human Virology

Open Access Oral presentation

The Molecular and Cellular Basis of Tumor Rejection After Vaccination With Mammary Adenocarcinoma Cells Transduced With the MHC Class II Transactivator CIITA

Lorenzo Mortara1, Paola Castellani2, Raffaella Meazza3, Giovanna Tosi1, Andrea De Lerma Barbaro1, Francesco A Procopio1, Luciano Zardi4, Silvano Ferrini3 and Roberto S Accolla1*

Author Affiliations

1 Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese

2 Laboratory of Cellular Biology, Istituto Nazionale per la Ricerca sul Cancro, Genova

3 Laboratory of Immunopharmacology, Istituto Nazionale per la Ricerca sul Cancro, Genova

4 Philogen, Advanced Biotechnology Center, Genova

For all author emails, please log on.

Retrovirology 2005, 2(Suppl 1):S55  doi:10.1186/1742-4690-2-S1-S55

The electronic version of this article is the complete one and can be found online at:


Published:8 December 2005

©

Oral presentation

CD8+ T cell responses are major players of tumor eradication in various vaccination protocols. However, an optimal stimulation of CD4+ T helper cells is required for both priming and maintenance of the effector CTL response against the tumor. In this study we show that the murine mammary adenocarcinoma cell line TS/A, a highly malignant MHC-II-negative tumor, is rejected in vivo if genetically engineered to express MHC-II molecules by transfer of the MHC-II transactivator CIITA. TS/A-CIITA cells are fully rejected by 93% of the syngeneic recipients and have a significantly lower growth rate in the remaining 7% of animals. Rejection requires CD4+ and CD8+ cells. CD4+ T cells are fundamental in the priming phase, whereas CTLs are the major anti-tumor effectors. All tumor rejecting animals are protected against rechallenge with the parental TS/A tumor. Immunohistochemical data at day 5 post-inoculation showed an higher infiltrate of CD4+ T cells in mice bearing TS/A-CIITA, than in mice bearing the TS/A tumor. Subsequently, from day 7 trough day 10, TS/A-CIITA tumors showed higher number of both CD4+ and CD8+ cells, dendritic cells, together with massive necrosis. The frequency of IFN-α-secreting splenocytes early after inoculations was also assessed by an ex vivo ELISPOT assay. Only the rejecting TS/A-CIITA animals showed an high frequency of IFN-α-secreting cells (between 80 and 120/106 splenocytes). Importantly, CD4 and CD8 depletion experiments revealed that at the time of tumor resolution the major cell population recognizing the TS/A-CIITA cells was of CD4 origin. This is the first example of successful tumor vaccination by genetic transfer of CIITA. These results open the way to a possible use of CIITA for increasing both the inducing and the effector phase of the anti-tumor response.