Breast Cancer Escape from T Cell Rejection Mediated by Indoleamine 2,3-Dioxygenase
Abstract
We performed research to support our hypothesis that human breast cancers have the capacity to evade a T cell mediated rejection at least in part by inducing the expression of an immunosuppressive enzyme called indoleamine 2,3-didoxygenase (IDO). Both of the objectives proposed in the original application were met. Using RT-PCR, we were able to demonstrate in a series of human breast tumors that IDO was expressed in the majority of these cancers. Furthermore, we made the interesting observation that the cells that invade breast tumors and tumor-draining lymph nodes that express IDO, as determined by immunohistochemical staining, are non-malignant mononuclear cells. This is supportive of our hypothesis that breast tumors induce the recruitment of DO-expressing immunosuppresive antigen presenting cells as a mechanism of evasion of an immune mediated rejection. The second objective of developing a mixed autologous tumor cell/lymph node cell model was also met. In this model a competitive inhibitor of IDO, 1 -methyl-tryptophan, was ineffective in augmenting an anti-tumor T cell response. Future experiments will include a T cell priming strategy in addition to IDO inhibition.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADB285481
Entities
People
- Scott J. Antonia
Organizations
- University of South Florida