Analysis of Tumor Antigen-Specific Tc1 and Tc2 CD8 Effector Cell Subpopulations as Potential Therapeutics Agents in the Treatment of Progressive Breast

Abstract

Abstract : Cytolytic CD8 T cells fall into two subpopulations based on cytokine-secretion. Type 1 CD8 cells (Tc1) characteristically secrete IFN-gamma, whereas type 2 CD8 cells (Tc2) secrete ILA and IL- 5. Using a TSA mammary carcinoma cell line, expressing HA as a surrogate tumor-associated antigen, we assessed the therapeutic effects of adoptively transferred HA tumor-specific Tc1 and Tc2 effector cells in mice with established malignancy. Both Tc1 and Tc2 subpopulations effectively delayed tumor cell growth and mediated tumor regression in mice with established malignancy. Flow cytometric analysis showed that donor cells accumulated at the tumor site and antitumor effects were highly tumor specific. First-line treatment with either methotrexate (MTX) or 5-Fluorouracil (5-FU) chemotherapeutic agents markedly enhanced the co- therapeutic effects of Tc2 effector cells. Whereas, MTX but not 5-FU, acted synergistically with corresponding Tc1 immunotherapy. Although effector cell therapies in combination with chemotherapy appeared markedly effective in delaying tumor growth they were non-the-less ineffective in establishing total long-term tumor eradication. These studies suggest a significant role for tumor-reactive Tc1 or Tc2 effector cell subpopulations in T cell-mediated antitumor responses and immunotherapy for the treatment of breast cancer and warrant further investigation as a potentially relevant anticancer therapy for breast cancer.