Both
melanoma and
glioma cells are of neuroectodermal origin and share common
tumor associated
antigens. In this article, we report that the melanocyte
differentiation antigen TRP2 (
tyrosinase-related
protein 2) is not predominantly involved in the
tumor rejection of a syngeneic murine
glioma. Although GL261
glioma cells endogenously expressed TRP2 and were lysed by TRP2 specific cytotoxic T cells (CTLs) in vitro, vaccinations with
TRP2 peptide-pulsed dendritic cells (DCs) could only induce minor antiglioma responses in a prophylactic setting and failed to work in a stringent setting where
vaccine and
tumor were administered on the same day. Further analysis revealed that TRP2 is not recognized by bulk CTLs after depletion of regulatory T cells which results in
tumor rejections in vivo. In contrast to
TRP2 peptide-pulsed DC,
tumor lysate-pulsed DCs were more potent as a
vaccine and completely protected mice from
tumor outgrowth in a prophylactic setting. However, the
vaccine efficacy of
tumor lysate-pulsed DC was not sufficient to prevent the
tumor outgrowth when
tumors were inoculated the same day. In this case, Treg depletion before vaccination was essential to boost antiglioma immune responses leading to the rejection of 80% of the mice and long-term immunity. Therefore, we conclude that counteracting the immunosuppressive
glioma tumor environment via depletion of regulatory T cells is a prerequisite for successful eradication of
gliomas after targeting multiple
tumor antigens by using
tumor lysate-pulsed DCs as a
vaccine in a more stringent setting.