gms | German Medical Science

Detection of micrometastatic bone marrow cells at diagnosis has been recently identified as an independent prognostic factor of primary breast cancer. It still remains unclear, why these disseminated tumor cells are able to survive in the bone marrow over years and are not eradicated by the local immune system. We could show recently that patients with primary beast cancer have an impaired T-cell activation of peripheral blood lymphocytes. Compared to healthy donors breast cancer patients have a highly significant reduction of CD 28,the important molecule for effective T-cell priming . Moreover we found a concomitant highly significant downregulation of TCR zeta on cytotoxic and T-helper cells, which determines the functional integrity of specific immune response by phosphorylation. These results were connected with Fas-induced apoptosis of peripheral blood lymphocytes. Based on these findings we now investigate in an ongoing prospective study the activation status of T-cells in the bone marrow, comparing breast cancer patients with tumor cell disseminated ( TCD-pos) and patients without tumor cell dissemination ( TCD-neg ). The T-cell activation status is analysed by multicolour flow cytometry and results were correlated with clinic- pathological prognostic factors by Mann-Whitney Wilcoxon U–test. So far 50 patients have been included in the study. Findings of T-cell impairment could explain the broken concept of immunesurveillance by resting disseminated tumor cells. This would give the opportunity for later reactivation of the disease although primary tumor was eradicated by surgery and adjuvant therapy. In this context we focused on T-cell priming , activation and apoptosis in order to find an explanation for antitumor dysfunction of T effector cells in the bone marrow.