Analysis of Tumor Antigen-Specific Tc1 and Tc2 CD8 Effector Cell Subpopulations as a Potential Therapeutic Agents in the Treatment of Progressive Breast Cancer
Abstract
Cytolytic CD8 T cells fall into two subpopulations based on cytokine-secretion. Type 1 CD8 cells (Tcl) characteristically secrete IFN-7,whereas type 2 CDS cells (Tc2) secrete TL-4 and IL-5. Using an aggressive TSA mammary adenocarcinoma cell line, expression HA as a surrogate tumor-associated antigen, we assessed the relative therapeutic effects of adoptively transferred HA tumor antigen-specific Tcl and Tc2 CD8 effector cells in tumorbearing mice at different stages of malignancy. Tcl, but not Tc2, subpopulations effectively delayed tumor cell growth and mediated tumor regression in mice with early (Day 7) stages of established tumor development. However, neither therapy was effective in more advanced (Day 21) stages of malignancy. Flow cytometric analysis showed that donor Tcl cells accumulated at the tumor site and antitumor effects were highly tumor antigen specific. Titration studies of Tcl effector cells showed that protection and therapy were dose-dependent in vivo. Tcl effector cells derived from IFN-7-deficient mice were less therapeutically effective than that of corresponding wild-type mice suggesting hat effector cell-derived IFN-7 played a significant role in Tcl-subpopulations in adoptive immunotherapy for the treatment for the treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA421028
Entities
People
- Mark J. Dobrzanski