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number of mtratumoral DCs, as previously described (Leveille et al., 2011), and increased CD8⁺ T cells. Therefore, treatment with VSV contributes to the establishment of an inflammatory milieu within the tumor that in tum leads to the recruitment of immune mediators. Ali three vimses containing an intact matrix protein (WT, Ge and Gór) induced a better CTL response against the surrogate tumor antigen gp33 compared to non-treated mice. It is important to point out that the differences in the immune response induced by the various VSV strains are not correlated with a disparity in their replicative ability but appears to be strictly resulting from their respective mutation(s).

To analyze the overall immune response induced by each VSV strain, we analyzed T celi responses against other tumor-associated antigens. The group of melanoma differentiation antigens includes proteins such as MART-1, gplOO, tyrosinase, gp75/tyrosinase-related protein (TRP)-l, and TRP-2 and are expressed by normal and malignant melanocytes both in human and mice (Parkhurst et al., 1998). However, in contrast to the immunogenic surrogate tumor antigen gp33, gplOO and TRP-2 are also expressed by normal melanocytes contributing, with other factors, to their poor immunogenicity. Furthermore, most of the antigen-specific T cells against these self-antigens are deleted or tolerized resulting in an inefficient immunity owing to preexisting tolerance (Bloora et al., 1997). CTLs against these antigens were detectable in our model but are unlikely to influence tumor regression at these level.

In a previous study, we found that the Gó and Gór mutants were highly cytopathic for B16 cells in vitro compared to the M mutant (Janelle et al., 2011). Here, we show that apart from inducing a strong antiviral CTL response, which may facilitate the concomitant uptake of infected tumor antigens, they also initiate a tumor-speciflc polyfunctional CTL response. Treatment with the Mmsir mutant failed however to generate a significant CTL response against the gp33 surrogate tumor antigen compared to non-treated animals. Nevertheless, treatment with all VSV strains significantly prolonged survival compared to non-treated mice. Unexpectedly, the increased functional anti-gp33 CD8⁺ T celi response induced by Gór treatment did not lead to a better tumor control whereas the poor anti-gp33 CD8* T celi response elicited by the Mmsir treatment did not worsen survival. Since differences between

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