NATURAL-KILLER-CELL ACTIVITY IN LONG-TERM SURVIVORS OF TESTICULAR CANCER - INFLUENCE OF CYTOSTATIC THERAPY AND INITIAL-STAGE OF DISEASE

Background. Patients with testicular cancer can be cured by cisplatin- based chemotherapy in many cases. Thus, concern about possible late to xicities of treatment is warranted. Methods. In this investigation, th e absolute number of natural killer (NK) cells according to their CD56 + phenotype, NK cell activity, and antibody dependent cellular cytotox icity (ADCC) were investigated in 29 patients with seminomas or nonsem inomatous germ cell tumors (NSGCT) a median of 31 months (range, 5-73 months) after termination of chemotherapeutic treatment. Results. No d ifference in the absolute number of NK cells, NK cell activity, and AD CC was found between patients with testicular cancer after either stan dard polychemotherapy consisting of bleomycin, etoposide, and cisplati n (BEP) or monotherapy with carboplatin and healthy control subjects. When patients were analyzed further using multivariate analysis, a sig nificant (P < 0.05) detrimental influence of BEP polychemotherapy vers us carboplatin monotherapy on NK cell activity was found. Moreover, NK cell activity also depended significantly (P < 0.05) on the time elap sed after chemotherapy was administered, but normalized with time. Bec ause the absolute number of NI( cells was not affected, is was assumed that polychemotherapy induced a functional defect. In a subanalysis o f patients with NSGCTs, metastases at diagnosis resulted in a signific ant (p < 0.05) and persistent stimulation of NK cell activity but not of ADCC. Conclusion. Cytostatic chemotherapy in patients with testicul ar cancer did not lead to compromised lytic effector cell function as assessed by NK cell activity and ADCC. However, a short, time-dependen t reduction was found that also depended on the intensity of chemother apeutic treatment. This finding related to the observation of a long-l asting stimulus of NK cell activity by initial metastases in patients with NSGCTs.