Excessive Prostaglandin E2 Production by Suppressor Monocytes in Head and Neck Cancer Patients

Abstract

The proliferative response of peripheral blood mononuclear cells (PBMC) to the mitogens PHA [phytohemagglutinin] and Con A [concanavalin 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 2 prostaglandin [PG] synthetase inhibitors (indomethacin or RO-205720 [D,L-6-chlor-.alpha.-methyl-carbazole-2-acetic acid]). This augmentation of immune response was independent of 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 yr 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 moncyte defined by a monoclonal antibody and purified with a fluorescence-activated cell sorter. Patients with epidermoid cancer of the head and neck have an abnormality of immunoregulatory monocytes that can contribute significantly to their depression of cellular immunity by elaborating PGE2. This abnormality could be partially corrected in vitro by incubating their PBMC with a prostaglandin synthetase inhibitor.