The activation of the CD40 pathway, mediated by either CD40L expressed in T cells or agonistic monoclonal antibody (anti-CD40 mAb), result in the upregulation of T cell co-stimulatory molecules (e.g., CD86, MHC) and the release of immunostimulatory and cytotoxic cytokines (e.g., IL-12, TNF-α) (Bennett et al., 1998; Ridge, Di Rosa, and Matzinger, 1998; Vonderheide, 2020), thereby enhancing cytotoxic T-cell activity impinging on cancer cell progression (Schoenberger et al., 1998; Quezada et al., 2004). The gene discussed is CD40LG; the disease is cancer.