Immature myeloid cells are continually generated in the bone marrow of healthy individuals, where they differentiate into mature myeloid cells (such as neutrophils and monocytes) without causing detectable immunosuppression. However, in cancer, immature myeloid cells are known to be recruited to the tumour microenvironment and to differentiate into myeloid-derived suppressor cells with a potent ability to suppress various types of immune responses. The precise mechanisms that drive this differentiation remain unclear. In the laboratory, myeloid-derived suppressor cell differentiation is known to be induced through the interaction of peripheral blood mononuclear cells with melanoma cell lines, and in the clinic, myeloid-derived suppressor cell numbers accumulate in the blood of melanoma patients in all stages of disease, including in early-stage I patients. However, the absolute requirement for these cells in supporting the establishment of melanoma is not well understood. In my project, I will investigate whether immature myeloid cells play a fundamental role in tumour development by exploring the direct and indirect capacity of immature myeloid cells to impact tumour establishment and early growth. Initially, I will deplete immature myeloid cells before tumour challenge to determine the effects of depletion on tumour establishment. Next, I will co-inject immature myeloid cells and suboptimal numbers of tumour cells to determine whether immature myeloid cells offer a growth or survival advantage to emerging tumours. Finally, I will use a Nanostring GeoMx digital spatial profiling discovery approach to define where immature myeloid cells are physically located within emerging tumours, which cell they interact with, and which growth and angiogenic factors they produce. These observations could lead to novel approaches to exploit these insights to stop melanoma at an early stage.