Key drivers include: 1) oncogenic pathways (PI3K/AKT, JAK/STAT), 2) inflammatory cues (IFN-γ), and 3) defective ubiquitination (FBXO38-related) promoting stability of the coinhibitory receptor while upregulating its cognate ligand in lymphocytes within the tumor microenvironment, exacerbating immune evasion (5). Here, AKT1 is linked to neoplasm.