Deviation of Anti-Tumor Immunity via IL-10 Production by Non-Small Cell Carcinomas

Lung cancer kills more individuals in Kentucky each year than anywhere else in the U.S. Whether a person survives lung cancer depends on a number of factors; however, the ability of a patient's immune system to attack his/her lung cancer is one important factor. Many lung cancer cells produce a hormone-like molecule called interteukin-10 (IL-10). This molecule is known to suppress many aspects of the immune system, but its role in the development of lung cancer is virtually unknown. We have developed a model in which mouse lung cancer cells express different levels of IL-10 and grow to form tumors when injected into mice. Using this model we have demonstrated that IL-10 alters the immune cell types and their state of activation within the tumor. We propose to use this model to determine if production of IL-10 by lung cancer cells suppresses the abilty of mice to develop an effective immune response against their tumors and whether IL-10 expression allows lung tumors to grow faster in mice and to spread more effectively to other tissues in the body. If the release of IL-10 by lung cancer cells is shown to inhibit the immune response against lung cancer cells and to enhance the growth and spread of the tumor in mice, it may suggest that therapies to control the production of IL-10 in lung cancer could enhance the ability of a patient to generate an immune response against their own tumor and subsequently increase the chances for survival for lung cancer patients. Consequentely, a final goal of this proposal is to neutralize IL-10 production by lung tumor cells in vivo to determine if a more effective anti-tumor response can be elicited in tumor-bearing mice. These studies will provide a framework for a future NIH grant application to determine if the poorer prognosis of lung cancer patients with IL-10-producing tumors is due to alterations in the immune response against their tumors. Findings from these studies will also allow us to determine if investigations into therapies which controllL-10 synthesis by lung cancers should be pursued in future studies. Finally, these studies will enable us to establish new interactions with other tumor immunologists and tumor biologists within the state of Kentucky and initiate the intellectual and scientific interactions that are necessary for development of successful NIH program project applications.