TNFRSF10B and neoplasm: Given that key factor determining tumor progression within spatiotemporal dynamics, is the infiltration and activity of cytotoxic T cells in the TME (Binnewies et al, 2018) and considering most preclinical DR5 agonist studies have relied on xenograft models lacking T cells and TME induced immunological changes in tumors (Motoki et al, 2005; Zhang et al, 2007; Camidge, 2008; Kaplan‐Lefko et al, 2010), our results support orchestration of an immune suppression by human and murine DR5 agonists.