In vitro anti-tumor activity of eosinophils from cancer patients treated with subcutaneous administration of interleukin 2. Role of interleukin 5

L. Rivoltini, V. Viggiano, S. Spinazze, A. Santoro, M. P. Colombo, K. Takatsu, G. Parmiani

Research output: Contribution to journalArticle

Abstract

Interleukin 2 (IL-2) administration is known to induce marked eosinophilia. To evaluate the potential role of eosinophils as anti-tumor effectors and to understand the direct or indirect effects of IL-2 on eosinophils, the physical and functional characteristics of eosinophils obtained during IL-2 therapy were compared with those of eosinophils obtained from the same patients before IL-2 administration, or from healthy donors. The treatment schedule consisted of subcutaneous (s.c.) injections of IL-2, and was performed in 7 patients with small-cell lung cancer (SCLC) in advanced stage. A marked increase of hypodense cells in peripheral blood was found to correlate with eosinophil activation in patients undergoing IL-2 therapy. Cytotoxic activity of eosinophils against allogeneic tumor cells (SCLC, K562 and melanoma lines), as assessed by direct and antibody (Ab)-dependent cellular cytotoxicity (ADCC), was markedly increased during IL-2 therapy. Conversely, eosinophils obtained before treatment, like those of healthy donors, lacked any activity against tumor cells. Sera from IL-2-treated, but not from untreated, patients, significantly improved the in vitro survival and anti-tumor cytotoxicity of eosinophils from healthy donors. Comparable effects were observed with eosinophils cultured with interleukin 5 (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF) and, to a lesser extent, by tumor necrosis factor-α (TNF-α), while no direct activity was mediated by IL-2. A 91% inhibition of eosinophil ADCC was found after pre-incubation of the sera of IL-2-treated patients with anti-IL-5 but not with anti-GM-CSF or anti-TNF-α Ab. IL-5 mRNA expression was detected in peripheral-blood lymphocytes (PBL) obtained 4 hr after IL-2 injection during the second and third week of IL-2 therapy. Phenotypic analysis of eosinophils from IL-2-treated patients showed enhanced expression of activation markers, including Fcγ RII (CD32), HLA-DR, CR3 (CD11b) and CRI (CD35). These findings suggest that a significant cytotoxicity against tumor cells can be mediated by eosinophils after indirect, IL-5-mediated in vivo activation by IL-2, and that eosinophils may be involved in the anti-tumor response(s) induced in vivo by IL-2.

Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalInternational Journal of Cancer
Volume54
Issue number1
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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