Abstract LB_C15: PI3Kδ/γ inhibitor as a novel immune-regulatory radiosensitizer

Abstract

Abstract Radiotherapy is known to augment anti-tumor immunity, yet its concurrent induction of immunosuppressive responses presents a significant obstacle to efficacious treatment. This study showed that a new PI3Kδ/γ inhibitor along with irradiation promotes systemic anti-tumor immunity and abscopal response by reducing activity of immune suppressive cells. The combination systemically decreased proliferation of regulatory T cells (Tregs) and enhanced the number of tumor specific CD8a+ T cells in tumor microenvironment, thereby leading to tumor regression. Interestingly, this effect lasts for 14 days after radiation and even causes distant tumors to regress, known as the abscopal effect. Moreover, molecular analysis shows that the combination treatment creates immune-stimulatory tumor microenvironment in tumors, suggesting that the combined therapy converts immune cold tumor into hot. These findings highlight the promise of using PI3Kδ/γ inhibitors to enhance anti-tumor immunity in solid tumors treated with radiotherapy, providing the evidence for the potential use of PI3Kδ/γ inhibitor as an immune-regulatory radiosensitizer. Citation Format: Yi Na Yoon, Jae-Sung Kim. PI3Kδ/γ inhibitor as a novel immune-regulatory radiosensitizer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_C15.