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Neutrophil-dependent tumor rejection and priming of tumoricidal CD8+ T cell response induced by dendritic cells overexpressing CD95L
- Source :
- Journal of leukocyte biology, 84(3), 713-720. FASEB
- Publication Year :
- 2008
- Publisher :
- Oxford University Press (OUP), 2008.
-
Abstract
- Overexpression of CD95 (Fas/Apo-1) ligand (CD95L) has been shown to induce T cell tolerance but also, neutrophilic inflammation and rejection of allogeneic tissue. We explored the capacity of dendritic cells (DCs) genetically engineered to overexpress CD95L to induce an antitumor response. We first found that DCs overexpressing CD95L, in addition to MHC class I-restricted OVA peptides (CD95L-OVA-DCs), induced increased antigen-specific CD8+ T cell responses as compared with DCs overexpressing OVA peptides alone. The enhanced T cell responses were associated with improved regression of a tumor expressing OVA, allowing survival of all animals. When DCs overexpressing CD95L (CD95L-DCs) were injected with the tumor expressing OVA, in vivo tumor proliferation was strikingly inhibited. A strong cellular apoptosis and a massive neutrophilic infiltrate developed in this setting. Neutrophil depletion prevented tumor regression as well as enhanced IFN-γ production induced by CD95L-OVA-DCs. Furthermore, the CD8+ T cell response induced by the coadministration of tumor cells and CD95L-DCs led to rejection of a tumor implanted at a distance from the DC injection site. In summary, DCs expressing CD95L promote tumor rejection involving neutrophil-mediated innate immunity and CD8+ T cell-dependent adaptative immune responses.
- Subjects :
- tumor
Fas Ligand Protein
Thymoma
Neutrophils
Ovalbumin
T cell
medicine.medical_treatment
Immunology
Genes, MHC Class I
Priming (immunology)
Apoptosis
chemical and pharmacologic phenomena
Cell Communication
CD8-Positive T-Lymphocytes
Transfection
Interferon-gamma
Mice
Immune system
Bone Marrow
MHC class I
medicine
Animals
Immunology and Allergy
Cytotoxic T cell
fas Receptor
Innate immune system
biology
Vaccination
Dendritic Cells
Skin Transplantation
Cell Biology
Immunotherapy
T cell response
Peptide Fragments
Mice, Inbred C57BL
Survival Rate
Retroviridae
medicine.anatomical_structure
Cancer research
biology.protein
Immunization
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 19383673 and 07415400
- Volume :
- 84
- Database :
- OpenAIRE
- Journal :
- Journal of Leukocyte Biology
- Accession number :
- edsair.doi.dedup.....f67cf9c477398bf78aa7cffeff48b16c