CONTRIBUTION OF SERUM INHIBITORY FACTORS AND IMMUNE CELLULAR DEFECTS TO THE DEPRESSED CELL-MEDIATED-IMMUNITY IN PATIENTS WITH HEAD AND NECK-CANCER

The immune system of patients with head and neck cancer is frequently depressed. Serum inhibitory factors and immune cell dysfunction are kn own contributors to this depression, but their relative roles are uncl ear. We have examined these factors to determine whether a common path way is involved. Is the defect an unresponding ''switched-off cell'' o r is it a remedial defect responsive to the removal of serum inhibitor y factors and/or to lymphokine restoration? Immune tests were performe d in 66 patients with high-stage head and neck cancer. Serum inhibitor y 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) ce ll 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 affini ty), were measured by flow cytometry through fluorescence-activated ce ll sorter analysis. Serum inhibitory factors were detected in more tha n 50% of the patients. Head and neck cancer sera significantly inhibit ing 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 r estored by increased IL-2 (1,000 U/mL) or a combination of IL-2 and IN F-alpha. Twenty-five percent of the patients were unresponsive to maxi mum lymphokine stimulation. Half of the patients had depressed express ion of the low-affinity IL-2 receptor (CD25). The cause of immune depr ession 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 fac tors by plasmapheresis and restoration of cellular defects by combined IL-2 with or without INF-alpha.