Cancer Immunology in an Inducible Model of Breast Cancer
Abstract
In the first year we have demonstrated rapid initiation of mammary metaplasia upon tissue specific stabilization of Beta-catenin, made fundamental observations on the role of the thymus and antigen specific regulatory T cells in suppressing active immune response against a defined antigen, and have embarked on improving tissue specific expression of our model antigen. Transgenic mice expressing low levels of HA, harbored antigen specific regulatory CD4 T cells. This was largely due to intra-thymic expression of this antigen. Adoptive T cell transfer experiments demonstrated that these cells proliferate as extensively as naive CD4(+) T cells upon immunization, without losing their phenotypic characteristics. Regulatory T cells eventually dominated the response expressing mostly IL-10 but not IL-2 or IFN-gamma. Thus, the capacity of suppressive T cells to expand upon antigen encounter is an essential component of immune regulation in vivo. These observations support the view that depletion or de-programing of regulatory cells prior to immunotherapy can he beneficial, in controlling cancer. We are currently pursuing vaccination strategies that could reverse the state of tolerance, by deprogramming tolerance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA420181
Entities
People
- Anja Siermann
- Fotini Gounari
- Khashayarsha Khazaie
- Ludger Klein
- Mei L. Chen
Organizations
- Dana–Farber Cancer Institute