Tumor infiltration by myeloid suppressor cells in response to T cell activation in rat gliomas

Abstract

We have recently reported that activation of tumor-specific T cells by subcutaneous vaccination with irradiated T9 glioma cells of syngeneic rats with a pre-existing, intracranial (i.c.) T9 glioma (T9+vaccination) promotes the mobilization of myeloid suppressor cells (MSC) which inhibit T cell function resulting in unregulated tumor progression. The current study investigated if this immunological paradigm could be recapitulated in T cell deficient rats, in other rat glioma models or using a dendritic cell (DC) vaccine. When nude rats were used in the T9+vaccination model, the level of MSC tumor infiltration remained low in vaccinated and control groups and there was no significant difference in tumor size between the groups. Increased tumor infiltration by MSC after vaccination with respective irradiated tumor cells was observed in the 9L, F98 and D74 gliomas. RT-2 tumors were markedly infiltrated with MSC regardless of vaccination. Enhanced tumor progression in response to immunization and T cell activation was observed in rats bearing F98 and D74 gliomas, although less pronounced than in the T9 model, and there was a trend for increased tumor size in the 9L glioma model. Increased MSC infiltrate and augmented T9 glioma growth were observed when DC pulsed with T9 cell lysate was used as a vaccine. These results suggest that MSC infiltration and unregulated tumor growth in response to vaccination is T cell-dependent; is not unique to the T9 glioma; and can be recapitulated with an alternate immunization approach.