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Peripheral blood natural killer cell activity in human breast cancer patients and its modulation by T-cell growth
Abstract:
The role of clinical status and chemotherapeutic intervention on native and inducible natural killer cell (NK) activity in breast cancer was ascertained by determining the K562 cytotoxicity capacity of peripheral blood lymphocytes. The level of NK activity in breast cancer patients receiving chemotherapy (n = 62) was significantly lower than that observed in patients currently receiving no treatment (n = 56) (at effector: target [E:T] ratios of 20:1, 10:1, and 5:1, 23.8%, 17.9%, and 12.1% versus 34.9%, 25.6%, and 15.9%, respectively; P less than 0.01, two-way analysis of variance). The absolute level of NK activity in peripheral blood of cancer patients on therapy was further reduced when compared with untreated patients and healthy controls when reductions in lymphocyte counts concomitant with chemotherapeutic intervention were included in calculations of NK activity. T-cell growth factor (TCGF) increased NK activity in all breast cancer patients and healthy controls with maximal stimulation of basal activity at a concentration of 10% (volume/volume [v/v]) TCGF. The percent stimulation of basal NK activity by TCGF was significantly greater in patients receiving chemotherapy (26.4%, 24.3%, and 19.0% at an E:T of 20:1, 10:1, and 5:1, respectively; n = 23) than in untreated patients (16.6%, 18.5%, and 18.9%; n = 21) and healthy controls (23.5, 18.6, and 8.1; n = 8) (P less than 0.05 and P less than 0.01, respectively, two-way ANOVA). The influence of soluble factors and agents in serum on peripheral blood NK activity was assessed by monitoring the effects of autologous plasma on basal and TCGF-stimulated NK activity. Autologous plasma at concentrations less than or equal to 10% (v/v) enhanced basal NK activity. Levels of inducible NK activity in the presence of either 10% TCGF, 5% plasma, or a combination of both were not significantly different in statistical comparisons of both the effects of inducer and therapeutic modality. At concentrations of plasma greater than 10% (v/v), progressively decreasing NK activities were observed. T-cell growth factor could partially reverse the inhibitions of NK activity by 25% autologous plasma. In 13 experiments, basal NK activity and NK activity in the presence of 10% TCGF, 25% autologous plasma, and a combination of TCGF and plasma were 27.6%, 46.0%, 16.3%, and 28.1%, respectively (E:T = 20:1). This study indicates that NK function is compromised in breast cancer patients receiving cytotoxic drug-therapy. The potential use of TCGF in adjuvant immunotherapy as a modulator of NK function has been demonstrated.(ABSTRACT TRUNCATED AT 400 WORDS)