IHC analysis of lung tissues revealed increases in arginase 1 (Arg1), a marker of immunosuppressive tumor-associated macrophages42, and α-SMA, a marker of cancer-associated fibroblasts43, in lung tissues from the NNK-exposed mice, while these NNK-induced increases were significantly attenuated in the Agt+/− mice (Supplementary Fig. 6a). This evidence concerns the gene ACTA1 and neoplasm.