Dendritic cells (DC(s)) are heterogeneous cells widely accepted as the key initiators of T cell immunity. To date, two major subsets of DCs are described: plasmacytoid DCs and conventional DCs. The latter consists of three lymphoid resident DC types found in all secondary lymphoid organs and three tissue-derived, or migratory, DC types that traffic from their tissue of origin to the lymph nodes. Subsets of these migratory DCs include epidermal-derived Langerhans cells and two dermal-derived DCs.
The aim of this study is to identify the DC subtypes responsible for presenting melanoma-derived antigens and to gain a mechanistic insight of such processes. To ascertain this information we utilize a mouse model of melanoma. Traditionally, such a model involves subcutaneous delivery of B16 cells. This results in tumour growth beneath the skin, a distal location to a host of distinct DC subsets resident in the skin, such as epidermal-derived LC.
This is in stark contrast to natural melanoma progression in humans. The etiology of this cancer clearly resides within the epidermal layer followed by vertical growth and dermal invasion. This certainly allows local epidermal- and dermal-derived DC to sample the malignant tissue before their migration to the tumour draining lymph node to initiate T cell immunity. Thus, to more closely mimic the human condition, we developed an orthotopic murine model of melanoma where tumour establishment and expansion is within the skin. We are using this novel model to dissect the complex immunosurveillance processes occurring during melanoma.