PIMREG and neoplasm: Here, the proteolytic activity of mainly CatB and CatS, despite their complex regulation and diverse activities, has an overall disastrous effect on anti-tumor immune responses by polarizing the myeloid APC in the TME from an M1-type toward an M2-phenotype, favoring the expansion and suppressive function of myeloid-derived suppressor cells (MDSC) and the related tumor-associated macrophages (TAM), resulting in the inactivation and depletion of cytotoxic CD8+ T cells and the expansion of Treg [5].