Blackwell Publishing Journal Backfiles 1879-2005
Background The role of cytotoxic cells in the control of cancer is now well established.Objectives To evaluate the expression of perforin and granzyme A in cytotoxic cells of patients with melanoma and to look for a link between this expression and natural tumour progression; to check if interferon (IFN)-α administration increased expression of cytotoxic mediators; and to evaluate if this increase was correlated with the antitumoral effect of IFN-α.Methods To determine in patients with melanoma the expression of the cytotoxic mediators perforin and granzyme A in peripheral blood natural killer (NK) and T cells, we used flow cytometry before and after IFN-α administration.Results Compared with healthy volunteers, we observed in 82 patients a low percentage of NK cells harbouring perforin [75% (95% confidence interval (CI) 70–79) vs. 92% (95% CI 89–95), P 〈 0·001] and granzyme A [48% (95% CI 41–55) vs. 73% (95% CI 66–81), P 〈 0·001]. By contrast, a high percentage of T cells, and particularly of CD56+ T cells, expressed perforin [56% (95% CI 41–71) vs. 28% (95% CI 18–38), P 〈 0·001], whereas a low percentage of CD56+ T cells expressed granzyme A [30% (95% CI 24–36) vs. 54% (95% CI 43–65), P 〈 0·001]. In untreated patients, the percentage of CD56+ T cells expressing granzyme A was higher in progressors than in nonprogressors [49% (95% CI 39–58) vs. 16% (95% CI 0–33), P = 0·003]. We followed cytotoxic mediator expression in 17 patients treated with IFN-α. IFN-α administration increased granzyme A expression in NK cells [44% (95% CI 27–61) and 65% (95% CI 54–76) before and after treatment, respectively, P = 0·010], rather than perforin expression, whereas expression of both perforin [46% (95% CI 30–62), and 58% (95% CI 44–73), P = 0·112] and especially granzyme A [27% (95% CI 14–40) vs. 45% (95% CI 26–64), P = 0·016] was increased in CD56+ T cells after IFN-α administration. Yet, this effect was not correlated with the clinical response to IFN-α.Conclusions Thus, the expression of cytotoxic mediators is altered in cytotoxic cells of patients with melanoma, and increased under IFN-α administration.
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