Unrestrained expansion of mutated melanocytes results in melanoma, the deadliest of skin cancers.  Fortunately, therapies developed in the last decade have significantly improved the outlook for many melanoma patients.  On the other hand, melanomas often fail to be completely eradicated when treated with these new pharmaceuticals, leading to undetected residual cells that can cause tumor relapse and drug resistance.   The primary objective of this proposal is to determine if a specialized cell of the immune system, the tissue resident macrophage, can act to protect melanoma cells against complete elimination during treatment.  By identifying and defining this particular melanoma-resident macrophage population, new avenues of research will open, especially in regard to understanding how protection is conveyed on a molecular level.  Most importantly, the data obtained through the studies outlined in this proposal could provide a new cellular target for the development of new therapeutics, with the hope and goal to combine with current treatments to ultimately eliminate all melanoma cells prior to the onset of recurrence.