Cancer Immunology in an Inducible Model of Breast Cancer
Abstract
Cancer patients can harbor significant numbers of CD8 and CD4 T cells with specificities to tumor Ags. Yet, in most cases, such T cells fail to eradicate the tumor in vivo, reflecting the partial or total compromise of tumor specific immune surveillance In the course of the past year we investigated the interference of Ag-specific CD4+CD25+ regulatory T (Treg) cells with the tumor-specific CD8 T cell immune response in vivo, by monitoring the homing, expansion and effector function of both subsets in draining and non-draining lymph nodes. The results show that CD8 cells expand to the same extent and produce similar levels of IFN-gamma in the presence or absence of Ag-specific Treg. Intravital imaging studies have revealed normal interaction of the cytotoxic T cells with HA expressing target cells within tumor draining lymph nodes, as well as release of granules by the T cells, but absence of any killing activity. Thus, Tregs abrogate CD8 T cell-mediated tumor rejection by specifically suppressing the cytotoxicity of expanded CD8 cells. The molecular mechanism of suppression involves TGF-beta since expression of a dominant negative TGF-beta receptor by tumor-specific CD8 cells renders them resistant to suppression and is associated with tumor rejection and unimpaired cytotoxicity, highlight the potential therapeutic sense of targeting TGF-beta receptor signaling, for enhancing anti tumor T cell responses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA437698
Entities
People
- Khashayarsha Khazaie
Organizations
- Dana–Farber Cancer Institute