Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy
Abstract
The purpose of this project is to study the immunomodulatory effect of Listeria on human dendritic cells (DCs) to optimize Listeria-based DC cancer vaccines. The project aims are: 1) Compare the activation and maturation of different human DC subsets in response to Listeria infection. 2) Define the induction of CD4+/CD8+ T-cell and NK cell responses to Listeria-activated DCs presenting a melanoma tumor-associated antigen. 3) Augment the immunogenicity of Listeria-activated DCs by inhibiting the immunosuppressive enzyme, indoleamine 2,3-dioxygenase. Key findings of the project include: 1) Listeria infection, including that mediated by attenuated strains, induces moDC, DDC, and LC maturation and activation. 2) Listeria-treated DCs are functionally active, potent stimulators of T cell proliferation. 3) Listeria-treated moDCs are potent stimulators of autologous T cell proliferation. 4) Listeria treatment, as compared with standard inflammatory cytokine stimulation, does not promote the over-expression of inhibitory markers on DCs. 5) Listeria treatment, as compared with standard inflammatory cytokine stimulation, does not potentiate the expansion of immune-dampening regulatory T cells by moDCs. 6) WT and ActA-deficient Listeria induce IDO to much greater extent than LLO-deficient Listeria. 7) Listeria-treated moDCs, without exogenous cytokine supplementation, may be potent stimulators of antigen-specific CTLs. Studies of the mechanisms of Listeria-induced immunity and optimization of Listeria-based DC vaccines are ongoing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2014
- Accession Number
- ADA612542
Entities
People
- David J. Chung
Organizations
- Memorial Sloan Kettering Cancer Center