Role of TNF family ligands and their receptors in immune destruction and escape of cancer

Description of projects available to graduate students:
Tumor necrosis factor (TNF) family ligands are type II cell membrane bound and secreted molecules, which are critically involved in a variety of vital functions, including embryogenesis, cell differentiation, development of the immune system, regulation of the immune responses, homeostasis, antiviral and anticancer defense. Recent studies have suggested that TNF family ligands might represent critical mediators of immune effector mechanisms which can control tumor growth. This concept has been strongly supported by our findings that human spontaneously tumoricidal effector cells, NK cells, express and simultaneously utilize to kill cancer cells several cytotoxic TNF family ligands. The present project will test three main hypotheses: 1. the mechanism of cytotoxicity mediated by multiple TNF family ligands is a general immune mechanism, which is employed not only by NK cells but also by other immune effector cells, including cytotoxic T lymphocytes, dendritic cells and activated B cells; 2. defects in this mechanism might cause in cancer patients a failure of the immune system to control cancer; and 3. reparation of these defects might reestablish cancer control. These studies are likely to lead to development of novel strategies for efficient immunotherapy of cancer. The project has been funded by NIH Oral Cancer Center Grant 1-PO DE13059.

Techniques graduate student will learn:
Purification of immune cell subsets, cell cultures of normal and cancer cells, in vitro generation and expansion of immune effector cells, RT-PCR, flow cytometry, ELISA, Western blotting, and various immune function assays, including cytotoxicity, proliferation and phagocytosis assays.