Interleukin-4 Drives Tumor-Associated Macrophage Polarization to Promote Tumor Gr

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DESCRIPTION (provided by applicant): Despite many advances in the battle against cancer, it remains a dreaded diagnosis and a leading cause of death in the United States. The rationale and hope for this proposed research is that any and all knowledge gained in understating how cancer progresses and infiltrates areas of the body brings, not only scientists, but the patients and public closer to achieving their common goal of complete eradication of cancers. The environment surrounding tumors is known to be one of smoldering inflammation and one cell type, known as a tumor-associated macrophage (TAM), prevalent in this environment has been shown to promote many aspects of cancer. TAMs foster tumor progression in multiple ways; they support new tumor blood vessel growth, tumor cell invasion, and even enhance metastasis. A key objective of this proposal is to understand the origin of the cellular signals that stimulate TAM's pro-tumor functions and how these signals act on TAMs. The proposed research is relevant to public health because understanding all of the sources and factors that influence cancer growth and metastasis - be they from the tumor or the body - will ultimately lead to discoveries of how to prevent tumors. Thus, this research is directly relevant to the NIH mission to seek fundamental knowledge that will reduce the burden of illness and lengthen life. The methods employed in order to achieve this goal will be to study tumor models in mice. Tumors will be generated that either do or do not secrete a certain signal, interleukin-4 (IL-4), and then these tumors investigated in mice that either do or do not have the ability to produce IL-4. Also, IL-4 and its effects on TAMs both with and without the IL-4 receptor will be studied to help discern how it might play a role in promoting cancer. The specific aims of this project are to determine the effects of IL-4 secreted from the tumor on tumor growth, metastasis, and TAMs and to understand how IL-4 signals to TAMs to achieve its pro- cancer consequences. It is expected that the impact of the results of this study will be in allowing researchers to target TAMs with future anti-cancer therapy from multiple avenues.