Effects of adjuvant chemotherapy on specific and non-specific immune mechanisms

Adjuvant chemotherapy is a well accepted concept in the treatment of breast cancer and has resulted in most clinical studies in a significant prolongation of the disease-free interval in certain subgroups of patients. However, very little is known about the late effects of adjuvant chemotherapy and its influence upon the function of a series of physiologic mechanisms. In the present paper, a review of our studies on the influence of adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluoruracil (CMF) upon the function of B, T and natural killer (NK) cells is given. It is shown that CMF adversely influenced primary antibody production following vaccination for a prolonged period of time after the termination of CMF treatment. In investigating T cell function, it was found that the administration of CMF led also to a similarly prolonged impairment of phytohemagglutinin (PHA-)stimulated soluble interleukin 2 receptor (sIL-2R) production and to a decrease in the proliferation of peripheral blood mononuclear cells following mitogenic stimulation with PHA. Finally, NK cell activity was found to be decreased for such a prolonged period of time after the termination of CMF treatment, too. We thus conclude that the administration of CMF in the adjuvant setting leads to a pronounced and prolonged impairment of certain immune mechanisms.