Cancer Immunology in an Inducible Model of Breast Cancer
Abstract
The growth of mammary tumors reflects the partial or total compromise of tumor specific immune surveillance in the tumor bearing host. By following the function and fate of T cells that recognize a defined antigen, it is possible to define the mechanisms involved in immune evasion by the tumor, and to open possibilities for targeted therapy. In the previous annual report we described an animal model of autochtonous mammary cancer. It was also reported that transgenic expression of an ectopic antigen (influenza hemagglutinin: HA) led to the generation of HA specific regulatory T cells, and that this was directly linked to the spurious intrathymie expression of this antigen. Over the course of the past year, we have made progress in generating a novel knock- in mouse line, that when crossed to tissue specific Cre mice allows for tight tissue specific expression of HA. We have also demonstrated that in the presence of physiological levels of tumor specific regulatory T cells anti- tumor cytolytic T cell responses are severely suppressed, while homing and proliferation of the T cells are apparently unaffected. Furthermore, we have shown that lymphonic expansion of CD8 T cells activates them and renders them resistant to regulation. These studies elucidate tolerance mechanisms that may be safeguarding immunogenic tumors against potentially lethal host T cell responses, and direct us to therapeutic strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425676
Entities
People
- Guoying Zhang
- Khashayarsha Shazaie
- Mei L. Chen
- Mikael Pittet
Organizations
- Dana–Farber Cancer Institute