Immune competent mouse models such as Alb-Cre Tg or ELF knockout which are genetically modified mice as well asB6C3F1 mice injected with a single dose of DEN or C57BL/6 mice receiving hydrodynamic tail-vein injections of HRASG12V and a short hairpin RNA that downregulates p53, HRASG12V and MYC, and HRASG12V and TAZS89A develop spontaneous orthotopic HCC that mimic very closely the conditions found in human tumors in terms of the tumor specific microenvironment and TGF-β moderated cross-talk with the cells of the immune system and in the microenvironment such as CAF. This evidence concerns the gene TGFB1 and neoplasm.