Down-regulation of CD28, TCR-zeta (ζ) and Up-regulation of FAS in Peripheral Cytotoxic T-cells of Primary Breast Cancer Patients

Abstract

Background: Several studies have supported the hypothesis that the concept of immuno-surveillance would not be effective in cancer patients. One reason for suppression of antitumor immunity may be attributed to immune impairment of T-lymphocytes, which extends beyond the tumor-microenvironment and might effect the peripheral blood. Therefore the aim of this study was to investigate the expression of immunoregulatory antigens in peripheral blood lymphocytes of primary breast cancer patients in comparison with healthy donors. Materials and Methods: The peripheral blood immune status of 61 patients with primary breast cancer was analysed by FACS-analysis. The different lymphocytic subpopulations were identified by intracellular/extracellular monoclonal antibodies in three-color flow cytometry. The distribution was compared to age-matched healthy female donors (n=29). Results: The expression of TCR zeta-chain, an important signal complex for T-cell activation and functional integrity of specific immune response, was significantly reduced in the cytotoxic specific T-cell population. Cytotoxic T-cells (CD3⁺/CD8⁺) also showed a down-regulation of CD28, the important ligand to the co-stimulatory molecule CD80 (B7.1) on antigen-presenting cells. Moreover, breast cancer patients had significantly more CD95 (FAS) expressing cytotoxic T-cells than their healthy counterparts (p<0.05). Conclusion: The significant up-regulation of CD95 and down-regulation of TCR zeta and CD28 in peripheral cytotoxic T-cells of breast cancer patients leads to the hypothesis of systemic immunosuppression, which could open the door for tumor cell dissemination via the blood stream and which is the subject of ongoing studies.