CD4 and neoplasm: Moreover, in in vivo preclinical tumor models, anti-PD-1 therapy can exacerbate high TGFβ signaling (Dodagatta-Marri et al. 2019) through activation of another checkpoint on exuberant T cell activation, the secretion of TGFβ1 from activated CD4+ T helper type 1 (Th1) cells (Donkor et al. 2011, 2012), as well as other mechanisms.