Analysis of Tumor Antigen-Specific Tc1 and Tc2 CD8 Effector Cell Subpopulations as Potential Therapeutic Agents in the Treatment of Progressive Breast Cancer
Abstract
Our overall objectives are to evaluate the antitumor effects and biological activities of Type 1 and Type 2 effector T cells in local and disseminated breast cancer. To date, we have developed and characterized in part, a murine breast cancer model that correlates with defined breast cancer classification stages of clinically progressive disease. Using the TSA adenocarcinoma, we assessed the phenotype and kinetics of tumor infiltrating lymphocytes (TIL) in mice challenged sc in the mammary region. At various times, tumors were extirpated and cell suspensions were analyzed using flow cytometric techniques. We show that T cells infiltrate the tumor site by day 7 following tumor challenge. Both CD4 and CD8 TILs were predominantly CD44(High) and expressed CD25, CD69, CD95 and CDl22 activation markers. Cytokine releasing profiles, as detected by intracellular cytokine staining, showed that activated CD4/CD44(High) and CD8/CD44(High) TILs produced elevated levels of IL-4, IL-10, GM-CSF and TNF suggesting that type 2 immune responses were elicited. Activated CD4/CD44(High) TIL numbers and frequencies reached peak levels at day 21 that markedly decreased by day 28 following tumor challenge.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA410762
Entities
People
- Mark J. Dobrzanski