Indomethacin sensitive suppressor-cell activity in head and neck cancer patients: The role of the adherent mononuclear cell

Abstract

Head and neck cancer (H&N CA) patients have known depression of cell-mediated immunity. There is suggestive evidence that prostaglandin (PCE+secreting cells may be a major factor. The authors have sought to determine the role of PGEZ-releasing monocytes-macrophages in this immune depression by determining the effects of adherent cell depletion and by measuring the effects of indomethacin, a PGEl synthetase inhibitor, on selected tests of lymphocyte function. Lymphocyte stimulation with phytohem-agglutinin (PHA) (T-cell stimulant) and Staph phage lysate (SPL) (B-cell stimulant) was done in the presence of varying concentrations of indomethacin; the effect of adherent cell depletion also was determined. The study population included 45 patients with localized or locoregional squamous CA of the H&N and 40 controls. Results included the following: (I) lymphocyte stimulation responses to PHA and SPL were generally depressed in the CA patients versus controls; (2) incubation with indomethacin produced bivalent effects in both controls and CA patients, depending on the concentration of indo-methacin and lymphocyte stimulant; incubation with optimum concentrations of indomethacin generally produced augmented responses in both study groups whereas high concentrations of indomethacin were suppressive: (3) the immune potentiating effects were not observed in older patients with advanced disease; and (4) removal of adherent leukocytes (mainly monocytes) also restored depressed lymphocyte responses. Although other factors also are operative, our data suggest that PGE2-secreting monocytes-macrophages may have a major role in the immune depression of H&N CA patients. Age and host effects of the cancer and the malnutrition common to these patients probably are involved also, although their singular contribution has not been measured. This depression is largely reversible by a PCE2 synthesis inhibitor, indomethacin, which suggests the potential value of in vivo administration of indo-methacin to H&N CA patients as an adjunct. Cancer 61A62-474, 1988. ATIENTS WITH head and neck cancer have known

An Inflammatory Cytokine Milieu is Prominent in Premalignant Oral Lesions, but Subsides when Lesions Progress to Squamous Cell Carcinoma

“…While studies have clearly shown that patients with HSNCC have profound immune dysfunction, very few studies have examined the immunological environment in premalignant oral lesions [4–6]. In addition, most studies with patients have focused on immune mediators, especially inhibitory mediators, in the peripheral blood rather than in the oral tissues [4,26].…”

“…Among the hallmarks of HNSCC is the profound inhibition of immune competence that is mediated in part by immunosuppressive cell populations including immune inhibitory macrophages, T-cells that are skewed toward a Th2 phenotype, Treg cells, myeloid-derived suppressor cells (MDSC) and the less mature CD34 + progenitor cells [4–6]. While systemic immune suppression is prominent in patients with HNSCC, immune alterations during the premalignant stage have not been well defined.…”

Increased recurrence and metastasis in patients whose primary head and neck squamous cell carcinomas secreted granulocyte-macrophage colony-stimulating factor and contained CD34+ natural suppressor cells

“…Studies of immune suppressor cells induced by other cancer types have focused on the peripheral blood, not on the intratumoral infiltrate (Gooding et al, 1995;Wanebo et al, 1993). Among the immune suppressor cells that have been identified in patients with HNSCC as well as other cancers are suppressive monocytes (Wanebo et al, 1988). Suppressor T-cell have been described in the peripheral blood of patients with breast and ovarian cancers (Yacyshyn et al, 1995) but there remains little support for their contribution to the immune suppressed state of patients with HNSCC cancers (Letessier et al, 1990).…”

“…Some human cancers induce suppressive T-cells that are inhibitory to immune functions, including anti-tumor T-cell reactivities (Chakraborty et al, 1991). Suppression of T-cell function in patients with HNSCC as well as with other cancers can also be due to monocytes or macrophages secreting the immune suppressive mediator prostaglandin E 2 (Wanebo et al, 1988). In one study with a small number of patients, HNSCC patients were treated with low-dose cyclophosphamide to reduce suppressor T-cells and with indomethacin to block the inhibitory activity of macrophages (Hadden et al, 1994).…”

Interleukin-1 beta and interleukin-6 release by peripheral blood monocytes in head and neck cancer

“…Based on these data and on the well-known impaired cytotoxicity and cytokine-production in peripheral blood mononuclear cells from head and neck cancer (Walter et al, 1985;Beauchamp et al, 1988;Wanebo et al, 1988), we investigated IL-l beta and IL-6 spontaneous and (LPS)-stimulated production by freshly isolated blood monocytes from patients with advanced head and neck squamous cancer (HNSC) in comparison to healthy subjects.…”