Excessive prostaglandin E₂ production by suppressor monocytes in head and neck cancer patients

The proliferative response of peripheral blood mononuclear cells (PBMC) to the mitogens PHA and Con A was significantly depressed in 86% of 45 head and neck cancer patients compared with 44 normal controls. This depression of immune competence was greatest in older patients and in those with more advanced disease stages. The abnormal mitogen responses could be restored toward normal (especially with Con A stimulation) by incubating the cells with either of two prostaglandin synthetase inhibitors (indomethacin or RO-205720). This augmentation of immune response was independent on other factors, including the primary tumor site, disease stage, treatment (surgery, radiation therapy, or chemotherapy) or the patient's age or race. The most likely explanation for this depressed level of immunocompetence was an excessive production of PGE₂ by suppressor cells. This was confirmed by the finding that PBMC from patients produced more PGE₂ than PBMC from normal individuals (8.4 ng/ml vs. 5.2 ng/ml, p = 0.002). This difference was greatest among patients less than 60 years of age whose cultured PBMC produced 91% more PGE₂ than controls (p<0.0007). Virtually all of the PGE₂ was produced by a population of monocytes defined by a monoclonal antibody and purified with a fluorescence-activated cell sorter. Patients with epidermoid cancer of the head and neck thus have an abnormality of immunoregulatory monocytes that can contribute significantly to their depression of cellular immunity by elaborating prostaglandin E₂. This abnormality could be partially corrected in vitro by incubating their PBMC with a prostaglandin synthetase inhibitor.