Homeostatic T Cell Expansion to Induce Anti-Tumor Autoimmunity in Breast Cancer
Annual rept. 31 Mar 2005-30 Mar 2006
SCRIPPS RESEARCH INST LA JOLLA CA
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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-peptideMHC 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-7antibody 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.
- Anatomy and Physiology
- Medicine and Medical Research