251 Uncoupling between receptor and G-protein by protein kinase A & C in the receptor-induced K +-current responses

Abstract

Fifty-one cervical nodes from 19 patients with advanced head and neck cancer were stimulated with phorbol dibutyrate and ionomycin (PDBu+Io) to determine the effect of such stimulation on the generation of cytotoxic T cells and whether this stimulation could hypass the need for autologous tumor stimulation. Lymphocytes stimulated with PDBu+Io demonstrated a sixfold greater in vitro expansion and significantly increased DNA synthesis. Whereas fresh lymphocytes displayed no cytotoxicity, stimulation with PDBu+Uo and culture in interleukin-2 (IL-2) led to significant cytotoxicity equivalent to that of lymphocytes stimulated with autologous tumor and IL-2. T cells with the greatest cytotoxicity were generated from patients with nodal metastases. In patients with stage IV tumors, effector cells demonstrating greater lysis of natural killer-resistant targets (Daudi cells) were associated with higher rates of recurrence (50% versus 12%, respectively, p<0.001). Stimulation with PDBu+Io augments growth and proliferation of lymphocytes from draining lymph nodes and preserves cytotoxicity without the need for autologous tumor. Excluding the need for antigenic stimulation by autologous tumor may prove useful in adoptive immunotherapy procedures.