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 and Con A 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 of other factors, including the primary tumor site, disease stage, treatment (surgery, radiation therapy, or chemotherapy) or the patients'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 less than 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 PMBC with a prostaglandin synthetase inhibitor.

Prognostic significance of cyclooxygenase-2 in laryngeal squamous cell carcinoma

“…It has been reported that in head and neck cancers, the majority of PGE2 measured is probably derived from host inflammatory or stromal cells. 27,28 Therefore, we cannot exclude that in COX-2 negative laryngeal SCC, PGE2 is produced by stromal and inflammatory cells. In addition, the prognostic significance of PGE2 levels in squamous cell carcinoma has not been adequately addressed.…”

Effect of prostaglandin E in multiple experimental models: V. Effect on tumor/host interaction

“…The most frequently reported immunologic abnormality in tumor-bearing patients is the decreased lymphocyte blastogenic response to mitogen stimulation. This impairment in blastogenesis has been reported in patients with head and neck, lung, and colon carcinomas and in patients with melanomas [3][4][5][6][7]14,15]. These studies also demonstrated that either addition of indomethacin to the lymphocyte cultures or removal of the monocyteimacrophage cells corrected the impairment in lymphocyte blastogenesis.…”

Current status and perspective of tumor immunotherapy for head and neck squamous cell carcinoma

“…The former inhibits the maturation of DCs and leads to inactivation of T cells (Siemert et al, 2021). The latter can suppress immune responses mediated by adaptive regulatory T cells (Balch et al, 1982).…”