For example, combining PI3K inhibitors with antibodies against the key immune checkpoint proteins PD-1/PD-L1 has improved antitumor responses in preclinical models by augmenting T-cell-mediated tumor cell killing and reducing immunosuppressive cell populations within the tumor microenvironment.527,528 AKT inhibitors can also increase the effectiveness of immunotherapies by promoting apoptosis in tumor cells and improving T-cell responses.529 Finally, immediate upstream regulators of mTOR can also serve as effective targets in combination therapies. This evidence concerns the gene CD274 and neoplasm.