The extracellular CD40L domain of the CSP is key to this double action approach since its receptor, CD40, is aberrantly expressed by many tumor cells, including RCC and melanoma, and is also expressed on tumor stroma, including antigen presenting cells, tumor-associated macrophages (45–48, 52) and tumor endothelial cells (40–42) (see Figure 1). The gene discussed is CD40LG; the disease is melanoma.