PI3Kγδ inhibitor plus radiation enhances the antitumour immune effect of PD-1 blockade in syngenic murine breast cancer and humanised patient-derived xenograft model

Triple combination therapy using a PI3Kγδ inhibitor, radiation therapy, and PD-1 blockade significantly delayed primary tumor growth and improved survival in mouse models.

• The treatment increased CD8+ cytotoxic T-cell fractions while decreasing immune-suppressive regulatory T cells, myeloid-derived suppressor cells, and M2 tumor-associated macrophages.
• In a humanized patient-derived breast cancer model, the combination therapy significantly delayed tumor growth and reduced immune-suppressive pathways.
• High ratios of regulatory T cells to CD8+ T cells and M2 to M1 tumor-associated macrophages were linked to poorer overall survival in patient data from The Cancer Genome Atlas.
• The findings suggest that targeting PI3Kγ and PI3Kδ may help address immunosuppression in tumors.

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