Evaluation of different effects of sera of breast cancer patients on the activity of natural killer cells.

In this study NK cell activity of 88 breast cancer patients in various stages of disease was investigated and a significantly lower activity in clinical stages I-III and especially in stage IV was found. Short term culture of peripheral blood lymphocytes (PBL) of these patients in medium RPMI 1640 with fetal calf serum (FCS) alone, gave a significant enhancement of NK cell activity and even more significantly if rhIL 2 was added to this medium. Considering the finding of diminished native NK cell activity in breast cancer patients and its augmentation by the above stated in vitro treatment, it was of interest to investigate the effect of sera of these patients, which represent the natural in vivo environment of NK cells, in order to see if the sera modulate the antitumor cytotoxic activity of these cells. In this sense, the in vitro treatment was performed on PBL of patients and controls with sera of patients with stages I-III (CaSa), stage IIIb (CaSb), stage IV (CaSm) and healthy control sera (HS). The results obtained for patients and controls show that compared to FCS all sera act in an inhibitory manner, but in contrast to HS, CaSa has a stimulative effect, while CaSb and CaSm give the greatest degree of NK cell inhibition of both controls and patients. Pooled metastatic sera (CaSp) and these sera after removal of molecules up to 8-10 kD by dyalisis (CaSd) show a similar degree of inhibition of NK cell activity of healthy controls and interfere in a reversible manner with NK cell activation by recombinant human interleukin 2 (rhIL 2). Analysis of soluble IL 2 receptor (s IL 2R) concentration, as a potential inhibitory factor in metastatic sera, rarely showed an increase. In conclusion, an impaired NK cell activity was found in patients with breast cancer. The impairment of NK cell activity progressed with the advancement of the disease. Along with this, the finding of a marked inhibitory effect of sera of breast cancer patients in advanced stage with metastases on the activity of NK cells and their activation by interleukin 2 may pose a problem for adjuvant immunotherapy with LAK cells and IL 2 and may indicate a need for prior plasmapheresis.