CD40 agonist antibodies exploit the following mechanisms to activate anti-tumor immunity: (1) activation of antigen-presenting cells (APCs) resulting in the generation of tumor-specific cytotoxic T cells that do not require helper CD4 T cells, (2) direct stimulation of macrophages that depletes tumor stroma, converting ‘cold’ tumors into ‘hot’ tumors, and (3) APCs activated by CD40 stimulation produce interleukins (IL) IL-12 and IL-15 facilitating NK cell-mediated tumor cell killing. The gene discussed is CD40; the disease is neoplasm.