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following infection while the Mmsir mutant has lost this ability (Janelle et al., 2013). This endoplasmic reticulum-resident protein has been shown to function as a phagocytosis signal for dendritic cells (Obeid et al., 2007) and is likely to induce immune-mediated celi death in vivo as well as to influence the antitumor immune response generated by these viruses.

Given the generał ability of VSV to induce tumor-specific cytotoxic T cells and the effects of VSV mutants on cancer cells in vitro, we sought to compare their immunomodulatory potential and correlate the antitumor response with survival in a B16/B16gp33 melanoma mouse model. Herein, we show that, while the Mmsir mutant induced the weakest gp33-specific antitumoral CD8⁺ T celi immune response compared to WT or G mutants, it could nonetheless induce a functional antitumoral CTL response that was very efficient at controlling tumor progression. We found that this discrepancy was not a matter of specific CD8⁺ T lymphocytes exhaustion sińce neither PD-1 nor PD-L1 blockade enhanced virotherapy in this system. However, we show that targeting and lysis by CD8⁺ T cells of tumor cells reflected the ability of Mmsir to upregulate class I MHC on tumor cells after infection.