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.