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Thomas J. Sayers, Ph.D.
Identification of Factors Involved in Tumor Cell Destruction by the Immune System
Biological therapy of cancer has not as yet provided significant therapeutic benefits for the majority of cancer patients. Nonetheless, some beneficial effects of immunotherapy have been seen in melanoma and renal cancer. These are assumed to be due to the activation of cells of the immune system. Yet, very little is known about how these cells or their products might mediate tumor cell destruction. Studies in our laboratory using several preclinical murine solid tumor models have determined that natural killer (NK) and T cells are critical for successful immunotherapy. These cells can mediate direct lysis of tumor target cells after cell-cell contact. Cytotoxic lymphocytes destroy tumor cells in vitro using 2 main mechanisms: (1) by the release of lytic granules from the lymphoid cells that contain toxic proteins including the pore-forming protein perforin as well as a family of enzymes known as granzymes (2) by the production of 'death ligands' of the TNF family which can trigger tumor cell suicide (apoptosis). The relative importance of these mechanisms for antitumor effects in vivo is being studied. Our current studies are also concentrated on identifying the molecular events underlying tumor cell death, with a focus on rapidly developing knowledge of mechanism(s) of apoptosis. We are studying a possible role for the 'death ligands' Fas-ligand, TNFalpha, and TRAIL in immune-mediated destruction of tumor cells in vivo and their role in controlling the development of tumor metastases. In addition, we are assessing the ability of some drugs to sensitize tumor cells to death ligands and the molecular basis of this sensitization. Our overall goal is to better understand the molecular events operating during tumor cell death. This knowledge should be useful in the rational design of agents to trigger these 'suicide' pathways in tumor cells.
This page was last updated on 2/22/2013.