Diminished in vitro-measured natural killer (NK) cell activity identifies a head and neck cancer patient at increased risk of death due to uncontrolled metastatic disease. Furthermore, measured activity is independent of standard staging techniques. Such observations suggest that the determination of natural immune status provides significant information regarding the clinical assessment of the head and neck cancer patient. Results point to the need to more clearly define the role of the natural killer cell in controlling the progression of autologous head and neck cancer. Through this project proposal the clinical significance of natural immunity within the head and neck cancer patient will continue to be developed. Its independent prognostic significance in relationship to established clinical prognostic variables will be tested utilizing multivariate statistical techniques. A clinical prediction rule defining the risk of distant metastases in head and neck cancer patients will result. The relationship of NK cell activity to the competition of NK cell subsets within the peripheral blood will be phenotypically defined by monoclonal antibodies and multiparameter flow cytometric means. The use of flow cytometric techniques will add to the clinical practicality of assessing natural immune status. Finally, the capacity of NK cells to lyse autologous head and neck cancer will be established. A model system for growth regulation of single cell preparations of autologous squamous cell cancer will be used. Growth kinetics will be quantitated using spectrophotometric analysis. The differential capacity of NK cell subsets to promote or control tumor growth will be analyzed. Results of this study will provide a basis for the use of flow cytometric analysis of NK cell subsets as a standard clinical assessment tool. Coupled with an understanding of how distinct NK cell subsets interact with the head and neck cancer, the expected individual clinical course would be better defined. An improved conceptual basis for the use of biologic response modification for the head and neck cancer patient would result.
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