GLIOBLASTOMA-ASSOCIATED CIRCULATING MONOCYTES AND THE RELEASE OF EPIDERMAL GROWTH-FACTOR

Monocytes/macrophages frequently infiltrate malignant gliomas and play a central role in the tumor-associated immune response as they proces s tumor antigen and present it to T-lymphocytes. Findings have accumul ated that peripheral blood monocytes leaving the cerebral circulation become microglial cells and vice versa and that monocytes/macrophages may stimulate malignant tumor growth by some unknown mechanism. Most m alignant gliomas express growth factor receptors, for example epiderma l growth factor receptor (EGFR). The aim of this study was to determin e whether peripheral blood monocytes of glioma patients release EGF, t he appropriate ligand of gliomncell membrane-bound EGFR. Long-term cul tured peripheral blood monocytes from 14 patients with malignant gliom as were compared to those from 12 controls (seven with nontumorous dis ease and five healthy individuals). Using an enzyme-linked immunosorbe nt assay for EGF, the EGF content of cell culture supernatants was det ermined at Days 7, 21, and 100 of culture. The EGF content (mean +/- s tandard error) of supernatants was 5.9 +/- 0.2 pg/ml/10(3) glioma mono cytes versus 1.3 +/- 0.1 pg/ml/10(3) control monocytes at Day 7 of cul ture, 22.9 +/- 0.8 pg/ml/10(3) glioma monocytes versus 1.8 +/- 0.9 pg/ ml/10(3) control monocytes at Day 21 of culture, and 23.4 +/- 0.7 pg/m l/10(3) glioma monocytes, and below detection levels for control monoc ytes at Day 100 of culture. Steroid treatment of glioma patients did n ot influence the EGF release of cultured monocytes. These data indicat e that glioblastoma-associated peripheral blood monocytes may be disti nct from those of healthy individuals. Moreover, this study indicates that subtypes of glioma-associated peripheral blood monocytes may supp ort immunosuppression and promote growth of malignant glioma by releas ing unusually high amounts of EGF.