Elevation of soluble interleukin-2 receptor in patients with non-small cell lung cancer treated with gefitinib.
OBJECTIVE
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 Blood samples were withdrawn from all patients before and after the administration of gefitinib and plasma soluble P-selectin, serum RANTES, and serum sIL-2R were measured by enzyme-linked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.


CONCLUSIONS
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.
Kanazawa
Shigenori
S
First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan.
Yamaguchi
Kazuyuki
K
Kinoshita
Yoshimi
Y
Komiyama
Yutaka
Y
Muramatsu
Mikiko
M
Nomura
Shosaku
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D015704:CD4 Antigens / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy*; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019007:P-Selectin / Q000097:blood; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000097:blood*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015704:CD4 Antigens; D018946:Chemokine CCL5; D019007:P-Selectin; D011799:Quinazolines; D015375:Receptors, Interleukin-2; D000077156:Gefitinib