Downregulation of CD28 and TCR- zeta (ζ) in peripheral T-cells of breast cancer patients – a defect in immunosurveillance?

Aims: The concept of immunosurveillance is not effective in cancer patients. One reason for sup-pression of antitumor immunity can be attributed to functional impairment of T- lymphocytes which extends beyond the tumor microenvironment and can effect the body systemicly. This general immune dysfunction related to peripheral blood lymphocytes could open the “ door “ for tumor cell escape/dissemination via the blood stream. Methods: We analysed the peripheral blood immune status of 64 breast cancer patients characterized by their prognostic factors. The different lymphocytic subpopulations were stained by intracellular /extracellular monoclonal antibodies for three color flow cytometry and appearance was compared to those in healthy donors. Results: The expression of TCR zeta-chains, an important molecule for the functional integrity of specific immune response, was significantly (p<0,005) reduced in the CD4+ and CD8+ subpopulation. Moreover T- cells of breast cancer patients showed a highly significant downregulation of CD28, the ligand to the costimulatory molecule B 7 on antigen-presenting cells. Conclusion: As CD28 is a quantitative support for TCR-ζ signalling and both molecules are essential for T cell activation, a concomitant downregulation could be an explanation for T cell impairment in breast cancer patients.