Reduced natural cytotoxic cell activity in patients receiving cisplatin-based chemotherapy and in mice treated with cisplatin

Abstract

In mice natural cytotoxic (NC) cells are known to play a role in the rejection of tumours that are sensitive to NC-mediated lysis. We have recently shown that in vitro human and murine tumour cells become more sensitive to lysis mediated by NC cells in the presence of the anti-cancer drug cisplatin. If NC activity plays a role in tumour surveillance in humans, then the ability of NC cells to eliminate tumours in patients treated with cisplatin would not only be dependent on cisplatin increasing the sensitivity of tumours to NC mediated lysis, but would also depend on the maintenance of high levels of NC activity during chemotherapy. Here we report that patients receiving chemotherapy that included cisplatin showed a time-dependent reduction in NC activity. NC activity was normal 1 day after treatment; however, 15 days after treatment patients had an eight- to 16-fold reduction in NC activity that returned to normal levels by day 21. The reduction in NC activity of patients was coincident with a reduction in circulating monocytes. Mice treated with only cisplatin showed a similar reduction in NC activity. Mice treated with cisplatin had a reduced level of NC activity that was first apparent 8 days after treatment, reached a nadir on day 15, and returned to normal levels on day 22.