Alteration in lymphocyte phenotype associated with administration of adjuvant levamisole and 5-fluorouracil

Abstract

Levamisole (LMS) and 5-fluorouracil (5FU) administered adjuvantly are effective in reducing the relapse rate following surgical resection of Duke's stage C colon carcinoma. It has been postulated that LMS acts to stimulate the immune system and that this is one mechanism through which this drug exerts its antitumor effects. In this study, peripheral blood mononuclear cells (PBMC) were analyzed in nine patients with surgically resected colon carcinoma prior to initiation of adjuvant LMS/5FU and at several subsequent times while patients were on therapy. Changes in lymphocyte phenotype and soluble interleukin-2 receptor (sIL-2R) between pre-study samples and samples obtained during adjuvant LMS/5FU were evaluated. Significant increases were seen in the proportion of PBMC expressing natural killer (NK) antigen CD56 (14.7 +/- 2.4% versus 18.1 +/- 2.6%; P < 0.05) and surface IL-2R (CD25; 0% versus 0.42 +/- 0.15%; P < 0.05), in sIL-2R (314 +/- 86 U/ml versus 736 +/- 173 U/ml; P < 0.05), and in the CD4:CD8 ratio (2.34 +/- 0.93 versus 3.47 +/- 1.23; P < 0.01). A significant decrease in the proportion of CD8+ PBMC (24.7 +/- 3.8% versus 18.8 +/- 2.6%; P < 0.01) and total CD8+ PBMC (537 +/- 118 versus 324 +/- 37; P < 0.01) was seen. The increase in CD56+ cells correlated with sIL2R levels (r = 0.46; P < 0.05). No changes were noted for CD3, CD4, CD5, CD14, CD16, CD19, CDw49a, or TCR delta. The greatest increase in CD56+ cells and the smallest reduction in CD8+ cells were seen in the subgroup of patients who remained disease-free following adjuvant chemotherapy. This study suggests that adjuvant LMS/5FU has significant stimulatory effects on the immune system, which correlate with patient outcome and may account at least in part for its clinical efficacy.