Elimination of regulatory T cells is essential for an effective vaccination with tumor lysate-pulsed dendritic cells in a murine glioma model

Autor: Erik Bennink, Oliver Grauer, Gosse J. Adema, Stefan Nierkens, Liza W.J. Toonen, Joannes F M Jacobs, Roger P.M. Sutmuller, Wendy W. C. van Maren
Rok vydání: 2008
Předmět:
Cancer Research
Time Factors
Regulatory T cell
medicine.medical_treatment
Cancer Vaccines
Immunotherapy
Adoptive
T-Lymphocytes
Regulatory
Mice
Random Allocation
Immune system
Antigen
Immune Regulation [NCMLS 2]
Translational research [ONCOL 3]
Glioma
medicine
Animals
Cytotoxic T cell
Antigen-presenting cell
Brain Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Interleukin-2 Receptor alpha Subunit
Immunotherapy
gene therapy and transplantation [UMCN 1.4]
Dendritic Cells
Immunotherapy
Dendritic cell
Flow Cytometry
medicine.disease
Intramolecular Oxidoreductases
Mice
Inbred C57BL
Pathogenesis and modulation of inflammation [N4i 1]
Disease Models
Animal
medicine.anatomical_structure
Oncology
Immunology
Female
business
T-Lymphocytes
Cytotoxic
Immunity
infection and tissue repair [NCMLS 1]
Zdroj: International Journal of Cancer, 122, 1794-802
International Journal of Cancer, 122, 8, pp. 1794-802
ISSN: 0020-7136
Popis: Contains fulltext : 70406.pdf (Publisher’s version ) (Closed access) 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.
Databáze: OpenAIRE
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