INHIBITION OF LYMPHOCYTE FUNCTION BY HEAD AND NECK-CARCINOMA CELL-LINE SOLUBLE FACTORS

Background: Immunosuppression in patients with head and neck cancer is well recognized. Previous investigations have demonstrated graded imm unosuppression that becomes more pronounced as lymphocyte activity is measured closer to the primary neoplasm. In fresh tumors, a soluble fa ctor has been identified that may partly account for the observed grad ed immunosuppression. Objective: To examine the effect of soluble fact ors produced by head and neck sqamous cell carcinoma cell lines on the generation of lymphokine activated killer cell cytotoxicity and perip heral blood lymphocyte proliferation induced by interleukin 2, concana valin A, and phytohemagglutinin. Design: Conditioned supernatant fluid s were generated in a 4-day incubation period, using 5 head and neck s quamous cell carcinoma cell lines, and were assayed for the ability to inhibit the generation of lymphokine activated killer cell cytotoxici ty and naive peripheral blood lymphocyte proliferation induced by inte rleukin 2, concanavalin A, and phytohemagglutinin. Results: All condit ioned supernatant fluids significantly inhibited the generation of lym phokine activated killer cell cytotoxicity relative to controls, and t his inhibition was dose dependent. In contrast, supernatant fluids fro m a myelogenous leukemic tumor cell line, K562, and an ovarian epithel ial cell line, SKOV-3, failed to inhibit cytotoxicity. Supernatant flu ids conditioned with head and neck squamous cell carcinoma cell lines also profoundly inhibited the naive peripheral blood lymphocyte prolif eration induced by interleukin 2, concanavalin A, and phytohemagglutin in. Conclusions: These studies demonstrate that the cell lines of head and neck squamous cell carcinoma produce soluble factors that inhibit lymphocyte function. Furthermore, these experiments suggest that the inhibition previously observed with enzymatically disaggregated fresh tumors is due to factors produced by the tumor cells rather than by ot her cells within the tumor matrix.