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International Immunology Advance Access published online on April 24, 2009
International Immunology, doi:10.1093/intimm/dxp034
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Irradiated CIITA-positive mammary adenocarcinoma cells act as a potent anti-tumor-preventive vaccine by inducing tumor-specific CD4+ T cell priming and CD8+ T cell effector functions

Lorenzo Mortara1, Valeria Frangione1, Patrizia Castellani2, Andrea De Lerma Barbaro1 and Roberto S. Accolla1

1 Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Via Ottorino Rossi, 9, 21100 Varese, Italy
2 Laboratory of Cellular Biology, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy

Correspondence to: Correspondence to: R. S. Accolla; E-mail: roberto.accolla{at}uninsubria.it

In the present study, we investigated the possibility to use irradiated, non-replicating class II transcriptional activator (CIITA)-transfected tumor TS/A cells as a cell-based vaccine. Eighty-three percent of TS/A-CIITA-vaccinated mice were completely protected from tumor growth and the remaining 17% displayed significant reduction of tumor growth. In contrast, only 30% of mice injected with irradiated TS/A parental cells were protected from tumor growth, whereas the remaining 70% of animals remained unprotected. Immunity generated in the TS/A-CIITA-vaccinated mice correlated with an efficient priming of CD4+ T cells and consequent triggering and maintenance of CD8+ CTL effectors, as assessed by adoptive transfer assays. Important qualitative differences were observed between the two cell-based vaccines, as TS/A-CIITA-vaccinated mice developed a CTL response containing a large proportion of anti-gp70 AH1 epitope-specific cells, completely absent in TS/A-vaccinated mice, and a mixed Th1/Th2 type of response as opposed to a Th2 type of response in TS/A-vaccinated mice. Finally, in TS/A-CIITA-vaccinated mice, a statistically significant reduction in the percentage and absolute number of CD4+ CD25+ T regulatory cells as compared with those of untreated mice with growing tumors (P < 0.001) or mice vaccinated with TS/A parental cells were observed. These results let to envisage the use of CIITA-transfected non-replicating tumor cells as a vaccination strategy for prevention and, possibly, adjuvant immunotherapy in human settings.

Keywords: CIITA, CTL, MHC class II, Th cells, Treg cells

Transmitting editor: L. Moretta

Received 12 January 2009, accepted 12 March 2009.


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