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Clinical Significance of Poor CD3 Response in Head and Neck Cancer¹

Department of Otolaryngology/Head and Neck Surgery, University of California Irvine College of Medicine [T. Y. S., S. K.], and Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center [T. Y. S., C. E. M., K-T. L., S. K.], Orange, California 92868; Departments of Otolaryngology/Head and Neck Surgery [N. N., G. H. Y.], of Immunology/Microbiology [W-Z. W.], of Medicine [J. E.], and of Pathology [W. S.], Wayne State University School of Medicine, Detroit, Michigan 48201; Biostatistics Shared Resource, Chao Family Comprehensive Cancer Center and the Epidemiology Division, Department of Medicine, University of California-Irvine, Irvine, California 92697 [C. E. M.]; and Karmanos Cancer Institute, Detroit, Michigan 48201 [W-Z. W., A. R., J. E., W. S.]

Purpose: The objective of our investigation was to prospectively study what the implications of an unresponsive CD3 receptor are on clinical outcome in advanced-stage head and neck cancer patients.

Experimental Design: Lymph node mononuclear cells were purified from cancer patients and stimulated with immobilized anti-CD3 in vitro for 8 days. Two populations were identified, nonresponders (NRs) with [³H]thymidinecounts per min (cpm) <3500 and responders (Rs) with cpm 3500. NRs and Rs were prospectively followed for a minimum of 24 months, and clinical outcomes were compared. Postoperative complications, length of hospitalization, toxicities associated with chemotherapy or radiation therapy, survival, and disease-free status were measured.

Results: Twenty-six patients were followed, of which 19 Rs {[³H]_X = 37,819 ± 24,979 cpm (mean proliferative count ± SD)} and 7 NRs ([³H]_X = 1,375 ± 1,102 cpm) were identified. There were no phenotypic differences in lymph node T-cell subpopulations (CD3, CD4, CD8, CD28, CD45RO) between groups. There was a 71% (5/7) incidence of recurrent cancer in NRs compared with 16% (3/19) in Rs; the median disease-free interval was significantly less in NRs (P = 0.03). The risk ratio of Rs to develop a recurrent cancer was 0.237 (95% confidence interval, 0.057–0.994), much less than for NRs.

Conclusions: Patients with an unresponsive CD3 receptor as measured by in vitro response to anti-CD3 monoclonal antibodies had a significantly higher incidence of recurrent cancer. Analyses using Cox proportion hazards models demonstrated that CD3 response was the single greatest predictor of reduced disease-free interval. This is the first prospective study to confirm the importance of regional lymph node mononuclear cell CD3 receptor function in head and neck squamous cell carcinoma patients for tumor control.

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