Functional significance of the protein CD40 in lung cancer
Abstracts
Initial Award Abstract |
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Lung cancer is the most common cause of death from cancer in the United States in both men and women. The single most important risk factor for this deadly disease is cigarette smoking. During the next decade, more than 1.5 million people will be diagnosed with lung cancer, the majority of whom will have advanced disease which cannot be treated by surgery. Current medical therapies for lung cancer, including chemotherapy and radiation therapy, do not greatly improve survival. New approaches to treating lung cancer are desperately needed. Research studying the body's own immune response to cancer cells may allow for the development of new treatments which enable the cells of the immune system to more effectively recognize and kill cancer cells.
The research described in this proposal serves to evaluate possible methods by which human lung cancer cells avoid attack by the immune system. Lung cancer cells may inactivate cells from the body’s immune system by using a protein called CD40. The CD40 molecule was first found on cells of the immune system (B cells) where it acts to coordinate a cascade of events to protect the body from invasion by bacteria, viruses, and other harmful substances. The function of CD40 in lung cancer is not known. Our recent research suggests that the presence of this molecule on these tumors may allow the cancer cell to avoid attack by cells of the immune system. This may be a means by which cancer cells hide from the immune system. If we alter the function of the CD40 molecule on these cancer cells, it appears that the tumor cells change in a way that may allow cells of the immune system to attack and kill these cancers. The studies outlined in this research proposal will evaluate these findings in greater detail to better understand why the cells of the immune system are not very effective in killing cancer cells. Through this evaluation, insight may be developed to help discover new ways to treat patients with lung cancer using the body's own immune system. |
Final Report |
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The research described in this proposal serves to evaluate possible methods by which human lung cancer cells avoid attack by the immune system. Many different lung cancer cells have been found to secrete an important molecule on the surface of their cells called CD40. This molecule is a protein that was first found on cells of the immune system called B cells where it coordinates immune responses to protect the body from invasion by bacteria, viruses, and other harmful substances. The function of CD40 in lung cancer is not known. Recent research has suggested that when this molecule is "activated" on lung cancer cells, it alters the appearance of these cells. These changes may allow the cells of the immune system to attack and kill the cancer cells. It appears that the CD40 molecule on these cancer cells in an "inactivated" state prevents the immune system from functioning properly. This may be a way that cancer cells avoid attack by the immune system. Through the studies outlined in this proposal, insight may be developed to help discover new ways to treat patients with lung cancer using the body's own immune system.
Many different types of human lung cancer cells were found to have the CD40 molecule on their cell surface. Our data showed that more that 50% of the lung cancer cell types that we evaluated had substantial amounts of this molecule. This finding was very interesting since this molecule is known to play an important role in the function of the immune system. Why is this molecule present on cancer cells? Does CD40 change the activity of these cancers? Does it protect these cells from attack by the immune system? Through experiments in the lab, we were able to "turn on" or "activate" the CD40 protein on these cancer cells and study the effect of this activation. It seems that cells with CD40 on their surface change their appearance after the CD40 is activated. These tumors actually increased the production of other proteins that are known to be very important in stimulating the immune system. This may allow these tumors to actually change the way the immune system functions. Other results from the studies in our lab suggest that the activation of CD40 in cancer cells may make these tumors more sensitive to chemotherapy.
These findings suggest that CD40 may play a role in cancer cell function, growth, and sensitivity to attack by the immune system. Further laboratory studies evaluating the role of CD40 in cancer may allow the development of better treatment for this deadly disease. |
