The strategy of using rAd to transduce immunostimulatory genes such as TAAs, costimulatory molecules [6, 137, 138], and cytokines such as (C-C motif) ligand 5 (CCL5), IL, interferon (IFN), GM-CSF, and tumor necrosis factor (TNF) [12, 139–144] has shown significant promise in enhancing tumor immunogenicity and 'firing up' the TME (Fig. 3). The gene discussed is TNF; the disease is neoplasm.