Functional and Phenotypic Analysis of Lymphocytes in Head and Neck Cancer

Abstract

We compared the phenotype and antitumor effector function of lymphocytes obtained from tumor tissues, lymph nodes, and the peripheral blood of patients with head and neck cancer. Freshly isolated tumor-infiltrating lymphocytes were deficient in CD4+ T cells in comparison with lymph node lymphocytes (LNL) and peripheral blood lymphocytes. A significantly higher CD4/CD8 ratio observed in LNL vs tumor-infiltrating lymphocytes and peripheral blood lymphocytes was attributable to both a significant enrichment in CD4+ T cells as well as a decrease in CD8+ T cells. The percentage of natural killer cells (CD3-CD56+) was uniformly low in both tumor-infiltrating lymphocytes and LNL. In patients with cervical metastases, LNL contained an increased proportion of CD16+ cells. Tumor-involved lymph nodes were not enriched in the CD8+C11b+ subset of T "suppressor" lymphocytes compared with uninvolved lymph nodes. Also, tumor-involved lymph nodes had significantly fewer CD4+ T cells than did uninvolved lymph nodes. In comparison with peripheral blood lymphocytes, freshly isolated tumor-infiltrating lymphocytes and LNL were depleted of cytotoxic effector cells, as indicated by low or absent cytotoxic activity against tumor cell targets. The ability to generate lymphokine-activated killer cells was significantly reduced in LNL in comparison with peripheral blood lymphocytes. In patients with head and neck cancer, depressed local and regional antitumor responses are associated with a deficiency of functional cytotoxic effector cells rather than an increase in suppressor T lymphocytes.