The mTOR-mediated cellular metabolism is implicated in the cancer cells’–TME interactions during the tumor progression and drug resistance, suggesting that phosphoinositide 3-kinase (PI3K)-/protein kinase B (AKT)-/mTOR-blockade may have the dual benefit of reducing the cells’ proliferation, migration, and survival, and enhancing the tumor immunosurveillance through both the downregulation of the immunosuppressive pathways and the activation of anti-tumor immune activities. The gene discussed is AKT1; the disease is cancer.