Homeostatic T Cell Expansion to Induce Anti-Tumor Antoimmunity in Breast Cancer
Abstract
We have previously shown using a mouse model of melanoma that homeostatic T-cell proliferation, a process occurring in response to lymphopenia and dependent on signaling by self-peptide/MHC and trophic cytokines, may promote effective anti-tumor autoimmunity if induced in conjunction with a tumor-cell challenge. 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 first year of this project indicated that (a) lymphopenia and the associated homeostatic T-cell proliferation can be effectively induced using T cell-depleting anti-Thyl antibodies; (b) lymphopenia-induced homeostatic T-cell proliferation inhibits subcutaneous tumor growth, lung metastasis and mortality in an ectopic model of breast carcinoma; (c) gamma/delta T cells, a lymphocyte subpopulation with significant anti-tumor activity, can also be induced to undergo homeostatic proliferation, and this requires depletion of both alpha/beta and gamma/delta T cell compartments and availability of either IL-7 or IL-15; (d) the anti-tumor response is diminished in aged mice, and this correlates with inefficient homeostatic T-cell proliferation; (e) homeostatic T-cell proliferation in aged mice can be restored by provision of the trophic cytokine IL-7.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA437175
Entities
People
- Robert G. Baccale
Organizations
- Scripps Research