Contribution of serum inhibitory factors and immune cellular defects to the depressed cell-mediated immunity in patients with head and neck cancer

Autor: Nichola Kouttab, Shashikant Mehta, Dilshad Blackinton, Harold J. Wanebo
Rok vydání: 1993
Předmět:
Zdroj: American journal of surgery. 166(4)
ISSN: 0002-9610
Popis: The immune system of patients with head and neck cancer is frequently depressed. Serum inhibitory factors and immune cell dysfunction are known contributors to this depression, but their relative roles are unclear. We have examined these factors to determine whether a common pathway is involved. Is the defect an unresponding "switched-off cell" or is it a remedial defect responsive to the removal of serum inhibitory factors and/or to lymphokine restoration? Immune tests were performed in 66 patients with high-stage head and neck cancer. Serum inhibitory factors were measured by incubation of heat-inactivated serum (10%) with phytohemagglutinin (PHA)-stimulated lymphocytes or natural killer (NK) cells using the K562 assay. Lymphokine-activated killer (LAK) cell cytotoxicity was measured (in the presence/absence of serum) using chromium 51-labeled Raji tumor cells cultured 5 days with interleukin-2 (IL-2) (100 or 1,000 U/mL) and/or interferon-alpha (INF-alpha) (100 U/mL). IL-2 receptors, CD25 or p55 (low affinity) and p75 (high affinity), were measured by flow cytometry through fluorescence-activated cell sorter analysis. Serum inhibitory factors were detected in more than 50% of the patients. Head and neck cancer sera significantly inhibiting the normal lymphocyte response to PHA (11 of 22 patients), as well as significantly inhibiting the NK response of normal lymphocytes and the functional expression of the IL-2 receptor. LAK cell function at low-dose IL-2 was depressed in 45% of the patients (9 of 20) and was restored by increased IL-2 (1,000 U/mL) or a combination of IL-2 and INF-alpha. Twenty-five percent of the patients were unresponsive to maximum lymphokine stimulation. Half of the patients had depressed expression of the low-affinity IL-2 receptor (CD25). The cause of immune depression in patients with head and neck cancer is multifactorial and is related to serum inhibitory factors, as well as to inherent cellular defects. Based on these data, we would suggest a therapeutic approach in selected patients that includes the removal of serum inhibitory factors by plasmapheresis and restoration of cellular defects by combined IL-2 with or without INF-alpha.
Databáze: OpenAIRE