PIK3CG encodes phosphatidylinositide-3-kinase gamma (PI3Kγ), a lipid kinase that phosphorylates PtdIns(4,5)P2 to generate PIP3, recruiting PH domain-containing proteins like AKT1 to activate cell growth, survival, and proliferation pathways. PI3Kγ functions as a molecular switch controlling immune responses: in macrophages, PI3Kγ-Akt-mTOR signaling inhibits NFκB while stimulating C/EBPβ, promoting immune suppression; conversely, PI3Kγ inhibition restores immunostimulatory responses and enhances CD8+ T cell activation 1. In acute myeloid leukemia (AML), PI3Kγ maintains leukemia stem cell self-renewal through AKT-NRF2-mediated pentose phosphate pathway activation, while remaining dispensable for normal hematopoietic stem cells 2. PI3Kγ also functions through noncanonical PAK1 phosphorylation to support AML cell survival and mitochondrial function 3. In B cells, PI3Kγ promotes antibody responses and antibody-secreting cell differentiation 4. Mechanistically, PI3Kγ inhibition or degradation sensitizes AML cells to standard therapies and reduces tumor burden 5. Additionally, myeloid PI3Kγ drives pathological neovascularization through SLIT-ROBO signaling, and PI3Kγ inhibition combined with radiotherapy promotes macrophage efferocytosis and antitumor immunity in pancreatic cancer 6. These findings establish PI3Kγ as a targetable node controlling immune suppression, leukemia stem cell maintenance, and tumor-associated macrophage polarization, with therapeutic potential across hematologic and solid cancers.