Targeted Disruption of Tumor-Derived Chemokine Synthesis and Reversal of Tumor-Induced Immune Suppression
Abstract
Chemokines play a pivotal role in the maturation of the immune system, and in the initiation, and maintenance of an immune response. Because of their key role in the immune response, the aberrant expression of chemokines can have a profound effect on the ability of T cells to respond to antigen. We have found that several breast cancer cell lines produced chemokines capable of recruiting T cells. However, instead of increasing anti-tumor immunity, the tumor-derived chemokines may have prevented an effective immune response by desensitizing T-cell chemokine receptors. Our hypothesis is that disrupting the synthesis of tumor-derived chemokines (using anti-sense technology) will remove tumor-induced immune suppression and enhance the immunogenicity of the tumor. In order to test this hypothesis we have generated stable clones that lack MCP-1 and RANTES production compared to the parental tumor cell line. Using these tumors we have found that both MCP-1 and RANTES impair the T cell response to the murine mammary carcinoma 4T1. Tumors that lack MCP-1 or RANTES elicited a better tumor-specific T cell response. Studies are underway to determine the extent of tumor immunity generated to a tumor that lacks both of these chemokines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418012
Entities
People
- Robert A. Kurt
Organizations
- Lafayette College