• Br. J. Dermatol. · Apr 2005

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

    • B Guillot, P Portalès, A Du Thanh, S Merlet, O Dereure, J Clot, and P Corbeau.
    • Service de Dermatologie and Laboratoire d'Immunologie, Hôpital Saint Eloi, 2 avenue Bertin Sans, F 34.295, Montpellier Cedex 01, France. b-guillot@chu-montpelier.fr
    • Br. J. Dermatol. 2005 Apr 1;152(4):690-6.

    BackgroundThe role of cytotoxic cells in the control of cancer is now well established.ObjectivesTo 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)-alpha administration increased expression of cytotoxic mediators; and to evaluate if this increase was correlated with the antitumoral effect of IFN-alpha.MethodsTo 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-alpha administration.ResultsCompared 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-alpha. IFN-alpha 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-alpha administration. Yet, this effect was not correlated with the clinical response to IFN-alpha.ConclusionsThus, the expression of cytotoxic mediators is altered in cytotoxic cells of patients with melanoma, and increased under IFN-alpha administration.

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