Elevation of soluble interleukin-2 receptor in patients with non-small cell lung cancer treated with gefitinib

Abstract

Purpose: We previously reported that plasma thromboxan B(2), soluble P-selectin, and serum regulated on activation, normal T-cell expressed and secreted (RANTES) were elevated after gefitinib treatment. We hypothesized that gefitinib could activate T-lymphocytes via activated platelets, and so we measured serum levels of soluble interleukin-2 receptor (sIL-2R) in patients medicated with gefitinib.

Methods: Twenty-one patients with non-small cell lung cancer (NSCLC) were entered into this study. All patients received gefitinib over 2 weeks without severe adverse effects. Blood samples were withdrawn from all patients before and after the administration of gefitinib and plasma soluble P-selectin, serum RANTES, and serum sIL-2R were measured by enzyme-linked immunosolvent assay. In addition, we carried out the basic study of the interleukin-2 receptor (IL-2R) expression on CD4(+) lymphocytes by RANTES.

Results: Plasma soluble P-selectin, serum RANTES, and serum sIL-2R levels increased significantly in patients receiving gefitinib treatment for 1 and 2 weeks. RANTES did not induce the expression of IL-2R on CD4(+) lymphocyte. However, the anti-CD3 monoclonal antibody-induced expression of IL-2R was enhanced by the addition of RANTES.

Conclusion: Our finding indicated that lymphocytes were activated by gefitinib treatment. We think that sIL-2R elevation after gefitinib administration may be a factor positively effecting patients with NSCLC. It is deemed possible that the effect of gefitinib is induced not only by its blocking of the tyrosine kinase of epidermal growth factor receptor but also by antitumor immunity via its activation of T-cells.

Fig. 1

Levels of plasma sP-selectin, serum RANTES, and serum sIL-2R in healthy controls and lung cancer patients. Each symbol represents an individual patient and bars represent the mean values of each group. P values are in comparison with healthy controls

Fig. 2

Serial changes in sP-selectin, RANTES, and sIL-2R in all patients undergoing gefitinib treatment. P values compared with before treatment. 1w and 2w denote 1 and 2 weeks after treatment, respectively

Fig. 3

RANTES up-regulates activation marker expression by anti-CD3-stimulated CD4⁺ T-cells. Peripheral CD4⁺ T-cells were cultured with medium for 8 h and then stimulated in medium supplemented with 1,000 ng/ml RANTES for 4 h. Subsequently, the T-cells were transferred to microtiter plates with or without coating with anti-CD3 monoclonal antibody and were cultured for 8 h. Expression of CD25 was measured by flow cytometry. Representative data from one of the five independent experiments are shown