In addition, reduced interferon response, low T cell abundance, poor T cell activity and a more immunosuppressive tumor microenvironment (enriched TGF-β signaling, hypoxia signaling) were observed in tumors with amplified genes in these two pathways, suggesting that hyperamplification in cell cycle/RTK-RAS-PI3K pathways may be a key point to drive anti-PD(L)-1 resistance through inducing both an immunosuppressive tumor microenvironment and malignancy hallmarks [40, 41, 44–47]. This evidence concerns the gene TGFB1 and neoplasm.