Homeostatic T Cell Expansion to Induce Anti-Tumor Autoimmunity in Breast Cancer
Abstract
In previous studies, we have shown that effective anti-tumor autoimmunity can be elicited if a tumorcell challenge is given in conjunction with homeostatic T-cell proliferation, a process occurring in response to lymphopenia and dependent on signaling by self-peptide/MHC and trophic cytokines. We are currently investigating whether this principle can be applied to mouse models of advanced breast carcinoma, and whether the anti-tumor response can be enhanced using selected T-cell subpopulations, cytokines and tumor-vaccines. The results obtained during the second year of this project indicated that (a) irradiation is more effective than T-cell depletion by antibodies in inducing anti-tumor responses mediated by homeostatic T-cell proliferation; (b) the frequency of T regulatory cells (Treg) increases during homeostatic proliferation, particularly in the presence of a growing breast carcinoma; (c) in vivo depletion of Treg cells enhances the anti-tumor effect of homeostatic T-cell proliferation on subcutaneous breast carcinoma; (d) homeostatic T-cell proliferation kinetics can be significantly accelerated by injection of IL-7 complexed with anti-IL-7 antibodies; (e) IL-7/antibody complexes potentiate the effect of homeostatic T-cell proliferation on breast carcinoma metastasis; (f) tumor cells at early apoptotic stages induce production of type I interferons by dendritic cell subsets and promote efficient antigen-cross presentation to specific T cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA456894
Entities
People
- Roberto Baccala
Organizations
- Scripps Research