The main molecular mechanisms that have been showed to impair infiltration of TME by immune system, and underlie the immune-excluded phenotype, include aberrant activation of the TGF-β or WNT/β-catenin pathways, dysfunctional metabolic conditions of the TME such as a high degree of hypoxia, low tumor neoantigens load and/or alterations in tumor antigen presentation mechanisms.33,34,36. Here, TGFB1 is linked to neoplasm.