The PI3K-Akt signaling pathway contributes to upregulation of the expression of immunosuppressive or metastasis-promoting genes such as those for PD-L1, cytotoxic T lymphocyte–associated protein 4 (CTLA4), colony-stimulating factor 1 (CSF1), and the CSF1 receptor (CSF1R) in cancer cells or microglia in the microenvironment of brain metastases [33] (Fig. 1b(h, i)). This evidence concerns the gene CD274 and cancer.