The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-alpha treatment

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Abstract
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.