PI3Kγ inhibition drives M1 macrophage differentiation and synergizes with PD-L1 blockade to improve survival in poorly immunogenic head and neck squamous cell carcinoma.

ABSTRACT:

Background

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally with high mortality rates, highlighting the urgent need for novel therapeutic strategies. We investigated the efficacy of combining phosphoinositide 3-kinase gamma (PI3Kγ) inhibition with programmed death-ligand 1 (PD-L1) blockade in a poorly immunogenic HNSCC model.

Materials and methods

Mouse bone marrow-derived macrophages (BMDMs) were differentiated and polarized in the presence or absence of the PI3Kγ inhibitor IPI-549 or culture supernatants from MOC2 cells treated with or without IPI-549. MOC2 cells were orthotopically injected into C57BL/6 mice, and treated with anti-PD-L1, IPI-549, combined anti-PD-L1 and IPI-549 or vehicle control. Tumor burden, survival, and immunolog

SUBMITTER: Jordanides PP 

PROVIDER: S-EPMC12758254 | biostudies-literature | 2026 Dec

REPOSITORIES: biostudies-literature