PROJECT SUMMARY Melanoma is a significant cause of morbidity and mortality in the U.S. and among military veterans. Having discovered an immune-vascular regulating pathway (DC- HIL/SD4) whose function can be manipulated to treat cancers, we will: (1) dissect its effects on immunity and vascularity in melanoma; (2) develop treatment targeted at a key carbohydrate component of the pathway; and (3) characterize changes in this component during melanoma growth and metastasis. Our results will improve current management of metastatic melanoma and potentially other cancers.