The most common proposed mechanisms of TGF-β-driven ICB resistance are CD8+ T cell exclusion via fibroblast differentiation and subsequent stromal remodeling and inhibition of CD4+ T helper cell differentiation to the immune-activating T-helper (Th)1 effector cell phenotype, as these conditions have been reproduced in various mouse tumor models and effectively treated by combined targeting of TGF-β and the PD-1/PD-L1 axis[149-152]. This evidence concerns the gene CD274 and neoplasm.