CHEMOTHERAPY-INDUCED DIFFERENTIAL CHANGES IN LYMPHOCYTE SUBSETS AND NATURAL-KILLER-CELL FUNCTION IN PATIENTS WITH ADVANCED BREAST-CANCER

To elaborate a rational approach to chemoimmunotherapy in humans, info rmation is required as to how current cytotoxic chemotherapy regimens modulate patients' endogenous immune cells. We have studied a group of 16 advanced breast cancer patients who received cyclical cytotoxic ch emotherapy (CMF-cyclophosphamide, methotrexate and 5-fluorouracil) and have documented the progressive differential effects of chemotherapy on endogenous immune cells as judged by changes in immunophenotype and absolute numbers of lymphocyte subsets, together with analysis of nat ural-killer-cell function. Cells with the immunophenotype of natural k iller cells and lymphokine-activated killer cells (NK/LAK cells) were well retained, but their function was suboptimal. Additionally, CD8 T cells were well preserved, but the numbers of CD4 T cells decreased wi th succeeding cycles of chemotherapy; B-cell numbers decreased rapidly from the first cycle of chemotherapy. These cellular changes in human s indicate defined and precisely timed windows of opportunity for intr oducing in vivo, simple and direct immune stimulation of the cells mod ulated by chemotherapy, with the possibility of improving therapy and survival in this disease. (C) 1993 Wiley-Liss, Inc.