Quantitation of natural killer cell function and risk of metastatic poorly differentiated head and neck cancer

Previous laboratory studies have suggested that natural immunity is a primordial defense mechanism against blood-borne metastatic cancer, its function being most effective against dedifferentiated, low-major-histocompatibility-complex-class-I-antigen-expressing tumors. In this clinical study, 263 previously untreated patients with squamous cell carcinoma of the upper aerodigestive tract were evaluated for natural killer (NK) cell cytotoxicity mediated by peripheral blood lymphocytes against K562 target cells. All patients were evaluated before treatment, underwent subsequent attempts at curative therapy in which they were initially rendered disease-free, and then followed longitudinally for clinical outcome. Using a Cox proportional hazards model, quantitated NK cell cytotoxicity was inversely related to subsequent death with disease (p = 0.05), regional metastases (p = 0.008) and distant metastases (p = 0.03). No relationship between NK cell function and local recurrence could be identified (p = 0.81). Patients were further stratified by degree of differentiation of their respective primary cancer. The prognostic implication provided as to risk of death with disease and progressive metastatic growth was confined to the population with moderate-to-poorly differentiated cancers. Conversely, its function was nonpredictive in patients with well-differentiated cancers; the latter cancers were observed to express higher levels of major histocompatibility complex-class I framework antigens. Results of this clinical study are consistent with previous laboratory investigations and suggest that, within humans, the NK cell functions in metastatic sites against more primitive cancers. Such findings may have implications in designing therapeutic strategies.