The transmembrane protein receptor 4-1BBis a member of thetumor necrosis factor (TNF) receptor superfamily andis involved in theco-stimulation of immunecells. 4-1BBis expressed in activated CD4 helper T cells, B cells, natural killer cells,natural killer T cells,dendritic cells,andactivatedendothelium1. Most regulatory T cells (Tregs)also express 4-1BB, but it remains unclear whether agonistic antibody treatmentexerts pro- or anti-suppressive effectonthese cells. 4-1BBenhances tumor rejectionbecause its engagement increases T cell proliferationandpro-inflammatory cytokine production. Combinationtherapy targetingboth 4-1BBandother immunecheckpoint proteins have been soughttoexpand its therapeutic potential and lower toxicity2.