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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
7R29CA046251-05
Application #
3458566
Study Section
Experimental Immunology Study Section (EI)
Project Start
1988-03-01
Project End
1994-02-28
Budget Start
1992-05-05
Budget End
1994-02-28
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Sacks, P G; Racz, T; Schantz, S P et al. (1994) Growth inhibition by interferon beta and gamma of MDA 886Ln monolayer cells and multicellular tumor spheroids. A differentiation therapy model for squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 120:1267-72
Schantz, S P; Dimery, I; Lippman, S M et al. (1992) A phase II study of interleukin-2 and interferon-alpha in head and neck cancer. Invest New Drugs 10:217-23
Schantz, S P; Ordonez, N G (1991) Quantitation of natural killer cell function and risk of metastatic poorly differentiated head and neck cancer. Nat Immun Cell Growth Regul 10:278-88
Schantz, S P; Clayman, G; Racz, T et al. (1990) The in vivo biologic effect of interleukin 2 and interferon alfa on natural immunity in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 116:1302-8
Schantz, S P; Racz, T; Ordonez, N G et al. (1990) Differential sensitivity of head and neck cancers to non-major histocompatibility-restricted killer cell activity. J Surg Res 48:154-64
Sacks, P G; Taylor, D L; Racz, T et al. (1990) A multicellular tumor spheroid model of cellular immunity against head and neck cancer. Cancer Immunol Immunother 32:195-200
Schantz, S P; Savage, H E; Brown, B W et al. (1990) Significance of C1q-binding macromolecules within the head and neck cancer patient. Cancer Res 50:4349-54
Racz, T; Sacks, P; Van, N T et al. (1990) The analysis of natural killer cell activity by flow cytometry. Arch Otolaryngol Head Neck Surg 116:440-6
Racz, T; Sacks, P G; Taylor, D L et al. (1989) Natural killer cell lysis of head and neck cancer. Arch Otolaryngol Head Neck Surg 115:1322-8
Schantz, S P; Savage, H E; Racz, T et al. (1989) Immunologic determinants of head and neck cancer response to induction chemotherapy. J Clin Oncol 7:857-64

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