The immunopharmacology of head and neck cancer: an update

Patients with head and neck squamous cell cancer have cell-mediated immune defects and anergy, which progress with disease. T-lymphocytopenia and dysfunction, monocyte dysfunction, prostaglandins, antigen-antibody complexes, serum and cell suppressive factors, radiation therapy and poor nutrition with zinc deficiency all contribute. Nevertheless, cell-mediated immunoreactivity to tumor is manifest in the majority of the patient's blood and regional nodes, and in the tumor itself by tumor-infiltrating lymphocytes. Lymphocytes from these sources cloned in the presence of interleukin-2 +/- tumor extracts show relatively specific cytotoxicity against squamous cell cancer. Humoral immunity is intact, and increased IgA and IgE levels and antibodies reactive to tumor antigens are common. Tumor-associated antigens detected in serum and tumor include carcinoembryonic antigen, tumor polypeptide antigen, squamous cell cancer antigens, tumor antigen-4 and various mucin antigens. The mucin antigens, in particular, can elicit T-cell responses. Humoral reactivity to such antigens is manifest in circulating immune complexes and immunoglobulin coating of tumor surfaces. Immunotherapeutic efforts in head and neck squamous cell cancer should logically employ T-cell adjuvants, contrasuppression and immunorestoration. Non-specific stimulation with bacille Calmette-Guerin (BCG), levamisole and other agents has not been successful. Encouraging results have been observed in limited trials with indomethacin and plasmapheresis. Early trials with local administration of low dosages of interferon-alpha, natural interleukin-2 and a natural interleukin mixture have produced partial and complete regressions with no toxicity and with intense leukocyte infiltration indicating cellular immunity. Efforts are needed to define the mechanisms and the antigens involved in these reactions. On the contrary, treatments with high dosages of recombinant interferon-alpha and interleukin-2 have yielded few responses and considerable toxicity. Combination strategies are discussed which may improve upon these initial immunotherapeutic effects of these low dose trials.